Mitochondrial effects on flower and pollen development

Mitochondrion 5 (2005) 389–402 www.elsevier.com/locate/mito

Review

Mitochondrial effects on flower and pollen development Bettina Linke, Thomas Bo¨rner * Department of Biology, Humboldt University Berlin, Chausseestr. 117, D-10115 Berlin, Germany Received 24 June 2005; received in revised form 4 October 2005; accepted 5 October 2005 Available online 4 November 2005

Keywords: cytoplasmic male sterility (CMS); mitochondria; flower development; programmed cell death; PPR protein; MADS-box

Contents 1. 2. 3.

4.

5. 6. 7.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CMS phenotypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mitochondrial genes involved in CMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. CMS genes may be generated by rearrangements in mitochondrial DNA . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Mitochondrial activity affects flower and pollen formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nuclear restorer genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Restoration at the DNA level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Restoration at the RNA level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Restoration at the metabolic level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Signals involved in nuclear—mitochondrial interaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Target genes in the nucleus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction As in other organisms, plant mitochondrial genomes contain only a few genes with most mitochondrial function encoded in the nucleus (Unseld et al., 1997). Mutations in mitochondrial * Corresponding author. Tel.: C49 30 2093 8142; fax: C49 30 8141. E-mail address: [email protected] (T. Bo¨rner).

389 391 392 392 394 395 395 395 396 396 397 398 398 398

genes may lead to severe defects in respiration. Such mutants are embryo lethal and can only be studied in chimeric plants that also contain wildtype mitochondria (Karpova et al., 2002 and Refs. therein). Other mutations lead to cytoplasmic male sterility (CMS), which has been described for about 150 plant species (Laser and Lersten, 1972; Kaul, 1988). Populations of several plant species have been described where gynodioecy is a common phenomenon, i.e. hermaphroditic (having male and

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female flowers) and female individuals (i.e. male sterile) co-exist, leading to speculations about potential adaptive advantages of CMS and gynodioecy, respectively. In plants, as sessile organisms, self-fertilization is common. CMS would force out-crossing and thus contribute to genetic diversity in natural populations (see Hanson and Bentolila, 2004, and Refs. therein). CMS plants have defective male flower organs but usually have normal female flower organs and exhibit no defects in vegetative parts. CMS phenotypes range from the inability to produce fertile pollen in otherwise normal flowers to drastically altered flower architecture. Altered flower phenotype or defects in pollen formation are presumed to be secondary effects of the mitochondrial mutation. As discussed below, the primary defect may be a reduction in the efficiency of respiration or the impairment of another mitochondrial function. Typically, one or more nuclear genes together with mitochondria bearing the CMS mutation, restore male fertility and are therefore termed restorer-of-fertility genes (short: restorer genes) (Touzet and Budar, 2004). At least some restorer genes reflect a co-evolution of mitochondrial and nuclear genomes. Other nuclear genes (or restorer alleles), the so-called maintainer genes, allow for the expression of the CMS phenotype and stabilize it (Kaul, 1988). Thus, expression of CMS is the result of a subtle interaction between mitochondrial and nuclear genes (Fig. 1). Consequently, CMS is often observed in the offspring of crosses between different species, or after fusion between protoplasts of different species/genera followed by regeneration of hybrid or ‘cybrid’ plants, i.e. when mitochondrial and nuclear genomes are combined that have not coevolved (Kaul, 1988; Zubko, 2004). The combination of a specific mitochondrial CMS gene with its nuclear restorer gene(s) is designated as ‘CMS system’ in this review. CMS has been genetically well-studied in many crop plants. Plant breeders and seed companies have been utilizing CMS since the 1960s for hybrid seed production. Hybrid seeds originate from crosses of certain inbred lines. CMS serves to prevent selfpollination in the line from which the seeds are harvested. Restorer genes are important to regain a fertile F1-generation from hybrid seeds, if the seed (as in corn) rather than a vegetative plant part (as in beet)

mitochondrial CMS genes nuclear restorer genes

mitochondrial function signaling nuclear target genes

fertile or male sterile flower

Fig. 1. CMS is attributed to a perturbed interaction between the mitochondria and the nucleus leading to defective flower development. Expression of mitochondrial CMS genes is thought to lead to impaired mitochondrial function. Products of nuclear restorer genes suppress the effects of mitochondrial CMS genes. The state of the mitochondria is signaled to the nucleus and results in activation or repression of nuclear target gene(s).

is harvested. Maize was the first crop for which CMS was extensively used in hybrid seed production. The T- (Texas-) cytoplasm can be used to generate a stable CMS phenotype in corn. At the end of the 1960s, more than 80% of hybrid corn seeds were produced in the USA by exploiting CMS caused by the T-cytoplasm. In 1969 and 1970 a fungal disease specifically affecting maize plants with the T-cytoplasm led to severe losses in crop yield. This ‘T-maize disaster’ led to investigations of the molecular mechanisms of CMS (Levings, 1993). Fig. 1 illustrates the CMS phenotype: (1) A mitochondrial CMS gene causes (slightly) impaired respiration or another alteration of the metabolic/ energetic state of mitochondria. (2) One or more nuclear restorer genes may suppress the effect of the mitochondrial CMS gene. (3) The state of mitochondria is signaled to the nucleus and (4) results in the activation or repression of target nuclear gene(s) that are needed for the formation of male flower organs and fertile pollen, respectively, or are involved in programmed cell death. In the following, we briefly describe CMS phenotypes and review the data concerning the four steps. For an extensive recent review the reader is referred to Hanson and Bentolila (2004).

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A

tapetum

pollen grains

B

391

filament anther

carpels

carpels

anthers filament petal sepal petal

D

C

brown anther

E

carpeloid

petaloid

Fig. 2. Flower architecture of a male fertile carrot flower, cartoon (A) and photograph (B). Fertile flowers have white petals (sepals are reduced) and intact reproductive organs; the male organs (stamens) consist of filaments and anthers with pollen grains. The tapetum surrounds the pollen. The female organs (carpels) are located in the floral centre. Phenotypes of carrot CMS flowers: The ‘brown anther’ CMS type (C) reveals defects late in male organ development. Filaments remain unrolled, anthers are brownish and early degrading; flower architecture is unmodified. Homeotic CMS types of the carrot develop ‘carpeloid’ (D) or ‘petaloid’ (E) flowers. Male organs are replaced by carpels (D) or petals (E). Arrows indicate aborted anthers (C) and replacement of stamens by carpels (D) or petals (E).

2. CMS phenotypes The perturbed nuclear-mitochondrial interaction of CMS plants affects flowers but usually not the other parts of the plant. The lifecycle of plants alternates between a vegetative (sporophytic) and a reduced gametophytic generation. After germination plants show continuous vegetative growth until flowers develop by formation of sepals, petals and the inner reproductive male and female organs (Fig. 2(A) and (B)). Flower organs are arranged in four concentric whorls. During early developmental

stages, primordial cells form hillocks in each floral whorl. Male organs arise in the third whorl by forming filaments and, at their tips, the anthers. Within the anthers (or pollen sacks) reproductive cells develop to microspores and finally into pollen grains (e.g. Scott et al., 2004). The inner cell layer of the anther, the tapetum, surrounds the microspores as a nutritive tissue (Fig. 2(A)). CMS-related abnormalities may involve different stages during the formation of male organs and pollen (Fig. 3). In many CMS types, the late steps of anther development or pollen maturation are impaired.

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392

Period of male organ / pollen formation premeiotic stages anther differentiation into midlayer, tapetum, microspore mother cells

anther shape becomes asymmetric

postmeiotic stages

meiosis

separation of meiocytes

microsporogenesis

tapetum becomes vacuolated

pollen wall formation

meiosis

formation of male generative cells (pollen mitosis)

tapetum primordial anther stage S5

pollen mitosis

stage

S6/7

locules

early floral organ differentiation

tetrade stage of microspores

microspore mother cells

individual pollen maturation (liberation from tetrads)

Carrot (carp/pet)

Canola/Rapeseed (nap/pol)

Petunia

Sunflower

T-maize

Common bean

homeotic-type

locules become fused or cease to develop at premeiotic stages; (Geddy et al., 2005)

premature tapetum degeneration (leptotene); (Conley and Hanson, 1994)

premature tapetum degeneration (pachytene); (Smart et al., 1994; Balk and Leaver, 2001)

premature tapetum abortion; (Warmke and Lee, 1977)

aberrant cytokinesis/ microspore liberation; (Johns et al., 1992)

of organ malformation at stage S6/7; (Linke et al., 2003)

liberation of mature pollen

S-Maize nostarch filling of haplospores; gametophytic pollen abortion; (Kamps et al., 1996)

Sorghum meiosis unaffected; development ceased before second pollen mitosis; (Tang et al., 1996)

Rice meiosis unaffected; normal up to second pollen mitosis; (Li et al., 2004)

Fig. 3. CMS affects different stages of male organ/pollen formation. Pollen formation can be divided into premeiotic stages, meiosis, postmeiotic stages and second pollen mitosis (formation of male generative cells; gametophytic stages).

The defect can appear before, during or after meiosis of pollen mother cells resulting in gametophytic or sporophytic CMS types (Kamps et al., 1996; Kempken and Pring, 1999). In many CMS plants, e.g. in the PET1type of CMS in sunflower (Smart et al., 1994; Balk and Leaver, 2001), tapetum function is impaired, seen as vacuolation or early degradation of tapetal cells. In other types of CMS, like in T-maize, effects become apparent only after meiosis. The mitochondria of tapetum and mid-layer of the anthers begin to degenerate and the plants reveal aborted pollen (Warmke and Lee, 1977). The CMS phenotype in carrot (type ‘brown anther’) becomes visible at the stage of anther development. The CMS flowers exhibit unrolled filaments, their anthers fail to dehiscence, become brownish and are degraded (Fig. 2(C); Struckmeyer and Simon, 1986). The general flower architecture is not altered in these CMS plants. Striking alterations in flower morphology are observed in another type of CMS plants in which early steps of flower formation are impaired. This type of CMS has

been studied in tobacco cybrids (plants regenerated from fused protoplasts with the nuclear genome of tobacco, Nicotiana tabacum, and the cytoplasm including mitochondria from another member of the Solanaceae, Hyoscyamus niger), in wheat, and carrot (Kofer et al., 1991; Zubko et al., 2001; Murai et al., 2002; Linke et al., 2003). Such CMS plants develop ‘homeotic’ flowers, in which male organs are replaced by another flower organ, e.g. by petals or even carpels, the female flower organs (Fig. 2(D) and (E); Thompson, 1961).

3. Mitochondrial genes involved in CMS 3.1. CMS genes may be generated by rearrangements in mitochondrial DNA In early studies on CMS, it was not known which cytoplasmic genes (plastid or mitochondrial ones)

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393

Table 1 Examples of mitochondrial sequences/genes associated with CMS Plant

orf

Flanking genes

Bean Petunia

pvs-orf239 pcf

atp9

Sunflower

orf522

atp1

Sorghum Radish kosena Brassica ogura Brassica pol

orf107 orf125 orf138 orf224

atp9 trnfM/atp8 trnfM /atp8 atp8/atp6

Brassica nap

orf222

Rice T-maize

orf79 urf-13

atp6 atp6/atp4

Mitochondrial genes/gene portions involved

References

atp1, 3 0 -regions of cob, orf239 atp9, coxII, urfS, orf143, and rps12, nad3 (co-transcribed) atp1, atp8

Mackenzie and Chase, 1990 Young and Hanson, 1987; orf143: Hanson et al., 1999 Horn et al., 1991; Moneger et al., 1994; atp8: Sabar et al., 2003 Tang et al., 1996 Iwabuchi et al., 1999 Bonhomme et al., 1991 Singh and Brown, 1991; Handa et al., 1995 L’-Homme et al., 1997

atp9 No similarities No similarities atp8, rps3, orf 224 and atp6 (co-transcribed) atp8 and nad5c (exon c), orf139 (co-transcribed) atp6, coxI rrn26, atp4, tRNAarg

Akagi et al., 1994 Dewey et al., 1986

Abbreviations: orf, open reading frame; urf, unidentified open reading frame; nomenclature of respiratory genes is according to yeast; nad, subunit of complex I; cob, coxI, coxII, subunits of cytochrome oxidase; the subunits of the ATP-synthetase F0/F1 components are indicated as atp1 (also designated as atpA), atp4 (former orf25 or orf221, gene product is similar to the beta-subunit of the F0 stalk; Heazlewood et al., 2003), atp6, atp8 (former orfB; Sabar et al., 2003); rrn26, 26S ribosomal rRNA; rps, ribosomal protein; trnfM, fMet-tRNA; the functions of orf139 and urfS are not known.

cause male sterility. By analyzing a mutant that lacks plastid ribosomes it could be shown that, at least in barley, none of the plastid genes are needed for the production of fertile pollen, implying that mitochondrial genes are responsible for CMS (Bo¨rner, 1985). Studies of T-maize demonstrated for the first time that the mitochondria (and not the plastids) contribute to CMS. An unusual open reading frame, called urf-13, was the first identified mitochondrial gene causing CMS (Dewey et al., 1986, 1987). Two nuclear restorer alleles, Rf1 and Rf2, are necessary and sufficient to suppress male sterility in T-maize (Laughnan and Gabay-Laughnan, 1983; Liu et al., 2001). The fungal toxin responsible for the abovementioned disaster interacts with the mitochondrial urf-13 gene product and forms hydrophilic pores in the inner mitochondrial membrane (reviewed by Rhoads et al., 1995). Examples of mitochondrial genes involved in generating CMS are compiled in Table 1. Direct evidence for their causal role in CMS is lacking as plant mitochondria cannot be genetically manipulated. In many cases CMS is caused by rearrangements of the mitochondrial DNA leading to new open reading frames (ORFs) composed of fragments derived from other genes and/or non-coding sequences (cf. Hanson and Bentolila, 2004; Schnable

and Wise, 1998; Kempken and Pring, 1999). It should be emphasized that other chimeric mitochondrial genes have been discovered that are clearly not associated with CMS or any other phenotype (e.g. Marienfeld et al., 1997). Thus, specific properties of the product of the ORF (transcript and/or protein) appear to be responsible for the CMS phenotype, as has been first demonstrated for urf-13 in T-maize (Abad et al., 1995; Rhoads et al., 1995; Sabar et al., 2003). Alternatively, mitochondrial gene/genome rearrangements may alter the expression of common mitochondrial genes coding for proteins involved in respiration/ATP synthesis, e.g. because of co-transcription with a new flanking gene (Table 1). The reason for the existence of chimeric genes and thus of many CMS systems is found in unusual features of the structural organisation of plant mitochondrial genomes combined with a high rate of recombination. Plant mitochondrial genomes are highly diverse in size and differ in structure and gene content from mitochondria of other organisms (Mackenzie and McIntosh, 1999; Burger et al., 2003; Knoop, 2004). Plant mitochondrial genes are spread over linear and circular DNA molecules of different sizes (Backert et al., 1997; Bendich, 1993; Oldenburg and Bendich, 2001). The mitochondrial

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genome of the model plant Arabidopsis thaliana contains 57 genes and consists of 367 kb. The major part of the genome is occupied by sequences of unknown function without detectable ORFs (Unseld et al., 1997; Marienfeld et al., 1999). Though different in size, the completely sequenced mitochondrial genomes of other higher plants have a similar gene content (Kubo et al., 2000; Handa, 2003; Clifton et al., 2004; Notsu et al., 2002; Sugiyama et al., 2005). Even closely related species and varieties of the same species show highly different gene arrangements. Intramolecular recombination as well as subdivision of the genome into (partly substoichiometric) subgenomic DNA molecules trigger rearrangements of the genes (Lonsdale et al., 1984; Palmer and Shields, 1984; Andre et al., 1992) and may create new ORFs from fragments of different genes and previously noncoding sequences. The fluidity of the genome structure due to replicative and recombinatory peculiarities offers the possibility to increase genetic variation and to retain genes in a silent but retrievable state when located on substoichiometric subgenomic DNA molecules. These processes are proposed to be controlled by the nuclear genome to contribute to plant mitochondrial evolution and the generation of CMS genes (Abdelnoor et al., 2003). The natural plasticity of the mitochondrial genome makes it difficult to identify CMS-associated gene regions. Comparative DNA, RNA and protein analysis of CMS and male fertile plants are usually not sufficient to identify the mitochondrial gene causing CMS since too many alterations are detected (e.g. Satoh et al., 2004). Additional data are needed on gene expression in mitochondria of sterile CMS plants in comparison with restored fertile plants having identical mitochondrial genomes. 3.2. Mitochondrial activity affects flower and pollen formation As in the case of human ‘mitochondrial diseases’ (Duchen, 2004), we have no satisfactory answer to the question of how defective mitochondria can bring about a specific phenotype and affect specifically the formation of male flower organs and pollen. There is no obvious correlation between the mitochondrial gene potentially involved in CMS and the specific CMS effects, i.e. the stage at which

flower development or pollen formation is impaired (Fig. 3). Mitochondrial alterations associated with the CMS phenotype include the production of novel proteins by chimeric ORFs, changes in the expression of otherwise unaltered genes, and the synthesis of altered mitochondrial proteins due to impaired RNA editing. Novel protein affecting mitochondrial function was first shown for the urf-13 product of T-maize that caused membrane disintegration by forming pore complexes (Levings, 1993). Altered expression of genes for respiration (Table 1) may affect ATP production and/ or other processes within mitochondria. A lowered ATP production (Bergman et al., 2000; Ducos et al., 2001; Sabar et al., 2003) or a reduced carbohydrate accumulation (Datta et al., 2002) were observed in ‘late stage’ CMS flowers. Oxidative stress during microsporogenesis was thought to induce a premature abortion of tapetal cells due to programmed cell death (PCD) in CMS sunflower (Balk and Leaver, 2001) and rice (Li et al., 2004). Tapetum-specific antisense expression of the mitochondrial alternative oxidase (Kitashiba et al., 1999) and of the mitochondrial pyruvate kinase E1a (Yui et al., 2003) caused male sterility in transgenic tobacco plants. In other CMS systems, altered RNA editing may cause male sterility. Editing of the mitochondrial atp6 transcript was strongly reduced in male organs (but not in shoots) in a CMS type of Sorghum (Howad and Kempken, 1997). Transcription, post-transcriptional splicing, processing and maturation of transcripts are more complex in plants than in humans or yeast, and editing of primary transcripts by partial changes of C residues into U and, less frequently, of U into C is very common (e.g. Binder and Brennicke, 2003; Brennicke et al., 1999). Interestingly, the modulated RNA editing of atp6 mimics point mutations of codons that cause severe disorders in humans (Kempken et al., 1998). Altered editing of the atp6 gene is also associated with CMS in rice (Iwabuchi et al., 1993). This principle can be used to design male sterile plants: gene products of an unedited atp9 gene induced male sterility in transgenic tobacco plants (Hernould et al., 1993, 1998). These data strongly support the view that insufficient mitochondrial activity prevents the formation of viable pollen. A likely, but not the only possible scenario is that CMS genes lead to impaired function

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of mitochondria that then cannot meet the high energy requirement or particular metabolic needs of certain steps of male flower and pollen formation. Other tissues are not affected because they do not need such a high mitochondrial activity, and/or because the CMS gene is only (highly) expressed in cells participating in the development of male flower organs (Conley and Hanson, 1994). Differences between the phenotypes of the particular CMS systems may thus be explained by the degree of impairment of mitochondrial function (depending on mitochondrial CMS gene and nuclear restorer gene/s) and/or by the developmental stage of flower, anther or pollen at which mitochondrial function is impaired (the CMS genes may be expressed differently in different tissues), and/or from the plant species. Flower development and reproduction are indeed energy-demanding processes requiring high respiratory rates. In response to these demands, the number of mitochondria and steady state levels of mitochondrial mRNAs increase several fold in developing flowers (Geddy et al., 2005; Huang et al., 1994; Mackenzie and McIntosh, 1999; Smart et al., 1994). In parallel, expression of nuclear genes encoding components required for mitochondrial function is also elevated (Landschu¨tze et al., 1995; Lohrmann et al., 2001; Schmidt-Bleek et al., 1997; Ribichich et al., 2001).

4. Nuclear restorer genes The nucleus may counteract the sterility-inducing factors of mitochondria. Restorer genes suppress the effect of mitochondrial CMS genes on the formation of anthers or pollen. Restorer genes can act by controlling copy number and transmission of subgenomic DNA molecules (Janska et al., 1998), posttranscriptional processing of mitochondrial transcripts (many examples), post-translational modification of CMS-related proteins (Sarria et al., 1998), and metabolic compensation of mitochondrial dysfunction (Liu et al., 2001). 4.1. Restoration at the DNA level A CMS type of the common bean (Phaseolus vulgaris) is associated with the accumulation of subgenomic DNA circles bearing the aberrant

395

pvs-orf239 sequence (Janska et al., 1998; Johns et al., 1992). These mitochondrial circles were reduced to extremely low substoichiometric levels in a restoring nuclear background. Thus, the restorer gene might be involved in replication/recombination thereby controlling the copy number of subgenomic molecules and thus of mitochondrial gene(s) involved in CMS (Janska et al., 1998). Genes involved in DNA (and RNA) metabolism of mitochondria are clustered on a segment of the Arabidopsis chromosome 3. Their physical linkage is thought to facilitate regulation of these genes (Elo et al., 2003). 4.2. Restoration at the RNA level The majority of the nuclear restorer genes seem to operate at the post-transcriptional level (e.g. RNA editing, processing, polyadenylation). There are numerous reports of reduced levels of transcripts of potential CMS genes in fertility-restored plants (e.g. Geddy et al., 2005). In T-maize, the product of the restorer gene Rf1 is essential, but not sufficient to restore fertility. RF1 leads to an increased splicing of the transcript from the T-urf13 region and in turn to a drastic reduction in the amount of the T-URF13 polypeptide (Wise et al., 1996). In Sorghum, restoration of fertility correlates with the internal splicing of orf107 transcripts and a concomitant reduction of a 12 kDa polypeptide presumed to be the product of this gene (Tang et al., 1996). The transcript processing sites in CMS-T maize and CMS of Sorghum share sequence features implying that particular sequence motifs within plant mitochondrial genes can serve as targets for nuclear-directed modulation of mitochondrial gene expression (Dill et al., 1997). Altered processing by endonucleolytic cleavage was described for the nuclear restorer background of Brassica CMS plants (Menassa et al., 1999). In restored CMS plants of sunflower, a tissue-specific polyadenylation of the CMS-specific orf522-atpA transcripts was observed (Gagliardi and Leaver, 1999). Polyadenylation of plant mitochondrial RNA has destabilizing effects (Kuhn et al., 2001). Thus, restoration by increased polyadenylation offers another mechanism to reduce aberrant CMS-related transcripts. Restorer genes have been cloned in Petunia (Bentolila et al., 2002), rice (Kazama and Toriyama, 2003; Akagi et al., 2004; Komori et al., 2004) and

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396 Table 2 Identified restorer genes Gene

Encoded protein/function

CMS system

Reference

Rf2 Rf Rf-1

Aldehyde dehydrogenase PPR protein/post-transcriptional regulation PPR protein/post-transcriptional regulation

T-CMS, maize PCF, petunia Boro, rice

Rfo, RFk1

PPR protein/post-transcriptional regulation

Ogura, Kosena, radish

Liu et al., 2001 Bentolila et al., 2002 Komori et al., 2004; Akagi et al., 2004 Brown et al., 2003; Koizuka et al., 2003

radish (Brown et al., 2003; Desloire et al., 2003; Koizuka et al., 2003). All of them encode mitochondrially targeted proteins with pentatricopeptide repeat (PPR) motifs (Table 2). Particularly in plants, PPR proteins belong to a large gene family comprising approximately 1% of the Arabidopsis genome (Small and Peeters, 2000). From about 450 PPR proteins in Arabidopsis, more than 60% are predicted to be targeted to mitochondria (Lurin et al., 2004). PPR motifs have been suggested to possess binding properties to proteins (Williams and Barkan, 2003) as well as to RNA (Small and Peeters, 2000). There are first indications for a role of Arabidopsis PPR proteins in specifying editing sites in chloroplast transcripts (Kotera et al., 2005). In humans, a PPRrelated protein with RNA-binding activity is associated with both nuclear and mitochondrial mRNAs and discussed as a potential candidate for a factor that may link nuclear and mitochondrial gene expression (Mili and Pinol-Roma, 2003). Mutant versions of this protein were shown to be associated with cytochrome c oxidase deficiency in humans (Mootha et al., 2003; Shadel, 2004). Hence, PPR proteins are good candidates for nuclear-encoded factors controlling distinct steps of transcript maturation in mitochondria. Many of them may turn out to be essential players in CMS systems. PPR proteins have been identified as targets of different miRNAs (e.g. Rhoades et al., 2002; Sunkar and Zhu, 2004). Small regulatory RNAs seem to occur also in plant mitochondria (Marker et al., 2002), but so far there is no indication for an involvement of regulatory RNAs in CMS. 4.3. Restoration at the metabolic level An entirely different mechanism of fertility restoration is proposed for the T-maize system. Here, a putative ‘biochemical restorer’ was identified.

The Rf2 gene was the first cloned restorer gene (Cui et al., 1996; Liu et al., 2001). It encodes a mitochondrial aldehyde dehydrogenase. Detoxification of toxic aldehydes by RF2 in the flower was suggested to complement RF1 action on gene expression in restoration of fertility (Liu et al., 2001; Liu and Schnable, 2002).

5. Signals involved in nuclear—mitochondrial interaction Nuclear control of mitochondrial gene expression in plants is well documented (e.g. Binder et al., 1996; Mackenzie and McIntosh, 1999) and plays a role in restoration of fertility as outlined above. However, retrograde signaling, i.e. how the state of mitochondria is signaled to the nucleus and affects flower/ pollen formation, is not understood. Therefore, only potential components of signaling pathways from plant mitochondria to the nucleus can be discussed here. In yeast and mammals, the interdependence between the functional state of mitochondria and gene expression in the nucleus is well studied and different ways of retrograde signaling from mitochondria to the nucleus have been described (reviewed in Poyton and McEwen, 1996; Burke et al., 1997; Butow and Avadhani, 2004; Kelly and Scarpulla, 2004). Transcriptional effectors depending on the metabolic state of mitochondria have been identified in yeast and mammalia, but not yet in plants. Interplay with the plastid as a third genome-bearing organelle makes interorganellar communication more complex in plants compared to non-green eukaryotes. There are indications for a cross-talk between plastids and mitochondria at the level of gene expression (Balmer et al., 2004; Hedtke et al., 1999), possibly reflecting

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the many-fold metabolic interactions between the two organelles (Raghavendra and Padmasree, 2003). Thioredoxins were found to act as mediators of the redox state between the plastids and mitochondria and might also participate in mitochondrial signaling to the nucleus (Balmer et al., 2004). Plastid-to-nucleus signaling has been intensively studied; ‘retrograde signals’ include intermediates of heme and chlorophyll biosynthesis, reactive oxygen species and redox state (reviewed by Pfannschmidt, 2003; Rodermel and Park, 2003; Gray et al., 2004). Reactive oxygen species are also considered to be signal molecules from plant mitochondria to other parts of the cell (Dutilleul et al., 2003; Mittler et al., 2004). Novel phosphorylated proteins as well as components of phosphorylation signaling pathways and calciumbinding proteins have been identified in plant mitochondria (Bykova et al., 2003; Heazlewood et al., 2004). It has recently been shown that mitochondrial deficiency triggers novel Ca2C-independent signaling pathways, leading to constitutive expression of genes for heat shock proteins. The retrograde signaling to the nucleus appeared to originate from a reduced mitochondrial transmembrane potential (Kuzmin et al., 2004). Further studies are needed to show which of these factors are involved in mitochondria-nucleus interactions that lead to CMS flowers.

6. Target genes in the nucleus Investigations into the mechanism of CMS have not supported the idea that mitochondrial genes are directly involved in flower or pollen formation. Instead, as outlined above, an impaired mitochondrial function is signaled to the nucleus, alters the expression of ‘target’ genes and leads indirectly, but specifically, to male sterility. Two groups of nuclear genes have been identified as potential targets: genes needed for the formation of male flower organs and pollen, as well as genes involved in programmed cell death. Studies on the homeotic type of CMS flowers (Fig. 2(D) and (E)) demonstrated a mitochondrial effect on the expression of specific nuclear genes for flower formation. The homeotic type of CMS flowers resembles nuclear mutants with defective genes for

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the specification of flower organs. Studies on these nuclear mutants led to the ‘ABC’-model of flower development. The ABC model explains how organs acquire and develop their appropriate identity: the four organ types are specified early in the floral meristem by the combined action of three classes of transcription factors encoded by A, B, and C genes (Weigel and Meyerowitz, 1994; Theissen, 2001). Class A and class C genes specify the identities of the perianth and reproductive organs, respectively, and act antagonistically to restrict each other’s function to their appropriate domains within the floral meristem. The class B products are active in domains where petals and male organs develop. Class A and B together determine petal identity and class B in combination with class C specify a proper formation of male organs. If class B and C genes are impaired in their function, male organs fail to develop and can be replaced by other organs which are specified by the remaining gene activities residing in the appropriate floral domains. Most products of A, B and C genes are transcription factors of the MADS-box family (Theissen, 2001). In several homeotic CMS flowers a reduced transcript accumulation of genes for MADS-box proteins with B-function was identified (Zubko et al., 2001; Linke et al., 2003; Hama et al., 2004; Geddy et al., 2005). Also SUPERMAN (SUP) seems to play a role in the generation of homeotic CMS flowers in tobacco (Bereterbide et al., 2002). Mutants of the SUP gene have extra stamens in their flowers and partially defective female organs (Bowman et al., 1992). The SUP gene encodes a nuclear transcription factor and is expressed in a limited region of stamen primordia and in the developing ovary during flower development (Ito et al., 2003). The studies on homeotic CMS flowers suggest that mitochondrial defects alter the expression of nuclear transcription factors which in turn activate or repress the transcription of genes specifying organ identity during flower development. Completely different is the effect of perturbed mitochondrial-nuclear interactions on later states in the formation of male flower organs, i.e. cases of malformation of anthers like in the ‘brown anther’ CMS type of carrot, or the failure to produce pollen as in CMS types of maize or sunflower (Fig. 3). In those cases, degeneration of one or more specific tissues has been observed. Plant cells may undergo programmed

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cell death (PCD), if they have to play only a temporal role during development, or if they are damaged or infected (Lam, 2004). In animals, the role of mitochondria in PCD is well documented (Goldenthal and Marin-Garcia, 2004; Orrenius, 2004). There is also evidence for an involvement of mitochondria in the programmed death of plant cells (reviewed in Lam et al., 2001; Vacca et al., 2004). Balk and Leaver (2001) reported that the PET1 mitochondria in sunflower (see Table 1, Fig. 3) cause premature PCD of the tapetal cells subsequently extending to other tissues of the anthers. Cytochrome c was released partially from the mitochondria into the cytosol of tapetal cells before the gross morphological changes associated with PCD were observed (Balk and Leaver, 2001). Further investigations have to determine if there is indeed a causal connection between PCD and perturbed mitochondria-nucleus interactions via alterations in the functional state of mitochondria.

7. Summary Cytoplasmic male sterility (CMS) is a maternally inherited phenotype characterized by the inability of a plant to produce viable pollen. This trait is a valuable tool used by plant breeders in hybrid seed production and by molecular biologists to study the interaction between the nuclear and mitochondrial genomes. CMS is caused by perturbed interaction of proteins encoded by mitochondrial and nuclear genes. Mitochondrial CMS genes of several crop plants originated from rearrangements of mitochondrial DNA sequences leading to aberrant gene products and/or altered levels of normal gene products. It is proposed that CMS genes primarily impair mitochondrial function that in turn results in male sterility. Nuclear restorer genes interfere with the expression of aberrant proteins or suppress by other means the effect of mitochondrial CMS genes thereby restoring fertility. Most of the identified restorer genes encode PPR proteins. As in the case of human ‘mitochondrial diseases’, it is not yet exactly understood how the mitochondrial defect can bring about a specific phenotype. Recently, first candidates of nuclear ‘target genes’ were identified, the expression of which is affected by CMS genes. They encode

MADS-box transcription factors specifying organ identity in flower development or proteins involved in programmed cell death. Those target genes are thought to be responsible for the defective formation of male flower organs and pollen.

Acknowledgements We are grateful to Sally Mackenzie, Arnold Bendich and Frank Kempken for critically reading this manuscript and valuable comments. The experimental work of the authors on CMS was supported by the Deutsche Forschungsgemeinschaft, Bonn.

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