- Email: [email protected]
Choline Theft—An Inside Job
Cell Host & Microbe
Previews Gomez, A., Espinoza, J.L., Harkins, D.M., Leong, P., Saffery, R., Bockmann, M., Tarralba, M., Kuelbs, C., Kodukula, R., Inman, J., et al. (2017). Cell Host Microbe 22, this issue, 269–278. Goodrich, J.K., Davenport, E.R., Waters, J.L., Clark, A.G., and Ley, R.E. (2016). Science 352, 532–535.
Kavanagh, K., and Dowd, S. (2004). J. Pharm. Pharmacol. 56, 285–289. Mark Welch, J.L., Rossetti, B.J., Rieken, C.W., Dewhirst, F.E., and Borisy, G.G. (2016). Proc. Natl. Acad. Sci. USA 113, E791–E800. Oppenheim, F.G., Salih, E., Siqueira, W.L., Zhang, W., and Helmerhorst, E.J. (2007). Ann. N Y Acad. Sci. 1098, 22–50.
Perry, G.H., Dominy, N.J., Claw, K.G., Lee, A.S., Fiegler, H., Redon, R., Werner, J., Villanea, F.A., Mountain, J.L., Misra, R., et al. (2007). Nat. Genet. 39, 1256–1260. Xu, D., Pavlidis, P., Taskent, R.O., Alachiotis, N., Flanagan, C., DeGiorgio, M., Blekhman, R., Ruhl, S., and Gokcumen, O. (2017). Mol. Biol. Evol. Published online July 21, 2017. http://dx.doi.org/10. 1093/molbev/msx206.
Choline Theft—An Inside Job Marina Mora-Ortiz1 and Sandrine Paule Claus1,* 1Department of Food and Nutritional Sciences, University of Reading, Whiteknights Campus, PO Box 226, Reading RG6 6AP, UK *Correspondence: [email protected] http://dx.doi.org/10.1016/j.chom.2017.08.017
Choline is a crucial methyl donor necessary for epigenetic regulation. In this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline-utilizing gut bacteria compete with their host for this essential resource, calling for a systematic consideration of gut microbial composition for personalized diet recommendations.
Choline is an essential nutrient abundant in diet, especially in high-protein-containing food such as eggs, red meat, soy beans, and wheat germs. It is critical for neurotransmission (as it is the precursor of the neurotransmitter acetylcholine), for epigenetic regulation via the synthesis of the major methyl donor S-adenosylmethionine (SAM), and is necessary to produce phosphatidylcholine, the ubiquitous phospholipid that ensures the integrity of cell membranes (Zeisel, 2000). Choline’s essential nature has been widely evidenced by studies in which choline deficiency results in abnormalities in epigenetic regulation and lipid metabolism (Lombardi et al., 1968; Pogribny and Beland, 2009). Following ingestion, some dietary choline is transformed by the gut microbial enzyme, choline trimethylamine (TMA) lyase, into TMA and acetaldehyde. TMA is then absorbed through the portal blood system and reaches the liver, where it is oxidized into trimethylamineN-oxide (TMAO) by the host flavin monooxygenase 3 (FMO3) (Baker and Chaykin, 1962; Lang et al., 1998) (Figure 1). In an elegant investigation published in this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline metabolism by gut bacteria plays a signif-
icant role in modulating host access to this resource (Romano et al., 2017). They first identified a choline-utilization gene cluster, cut, in a strain of E. coli (MS 200-1) isolated from the ileum of a healthy human donor. They show that this ‘‘type II’’ cut gene cluster encodes all the proteins required for anaerobic choline metabolism, including CutC and CutD, the choline-TMA lyase and its activase, respectively. Inspection of the genetic context of the cut gene cluster in g-Proteobacteria (of which E. coli is a member) allowed them to identify other genes potentially linked to choline usage absent in the type I cut cluster, which is abundant in Firmicutes, Actinobacteria, and d-Proteobacteria. Romano et al. (2017) then confirmed the role of the E. coli cut gene cluster in choline metabolism by knocking out cutC and cutD. These mutants were unable to grow on a restricted medium containing choline as the sole carbon source and failed to convert choline into TMA, demonstrating their essential involvement in TMA production from dietary choline. Next, they determined that the respiratory electron acceptors fumarate, nitrate, DMSO, and TMAO supported bacterial growth on choline as a carbon source in anaerobic conditions.
Given that nitrate is known to be released into the lumen during gut inflammation and that some E. coli sp. use it as an electron acceptor during anaerobic growth, Romano et al. (2017) hypothesized that the bacterial strains able to couple nitrate respiration with choline usage could bear an evolutionary advantage in the inflamed gut as previously suggested (Winter et al., 2013). Romano et al. (2017) further hypothesized that choline-consuming bacteria may have a significant impact on host choline-utilization pathways. To test this hypothesis, they developed a gnotobiotic model consisting of adult germ-free mice associated with a simplified gut microbiota composed of five bacteria common in the human gut that are unable to metabolize choline and added either a wild-type choline-consuming E. coli (CC+) or a cutC knockout (DcutC) non-choline consuming mutant strain (CC ). Deletion of the cutC gene significantly impaired E. coli colonization, suggesting that cholineconsuming E. coli receive a fitness advantage in vivo and that choline metabolism modulates the composition of gut bacterial communities. Importantly, CC+ colonization resulted in an altered host plasma metabolome, in which circulating levels
Cell Host & Microbe 22, September 13, 2017 ª 2017 Published by Elsevier Inc. 253
Cell Host & Microbe
Previews
Figure 1. Host-Gut Microbiota Co-metabolism of Choline Most of the daily intake of choline is readily absorbed in the upper-gastrointestinal tract. From there it is used directly by the liver as a methyl donor into the methylation pathway, which contributes to the endogenous synthesis of trimethylamine (TMA) and trimethylamine-N-oxide (TMAO). Unabsorbed dietary choline can also be metabolized by gut bacteria into TMA by TMA-lyase, which is encoded by the bacterial cut gene cluster. Some gut bacteria can oxidize TMA into TMAO, both of which can also be degraded into dimethylamine (DMA), methylamine (MA), and ammonia (NH3). Alternatively, TMA can be absorbed by the portal blood system and be further oxidized into TMAO by the hepatic flavin monooxygenase 3 enzyme. SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; THF, tetrahydrofolic acid; BHMT, betaine homocysteine S-methyltransferase; FC, folate cycle.
of metabolites involved in the methylation pathway (i.e., choline, betaine, methionine, dimethylglycine, and methionine sulfoxide), and therefore in the production of SAM, were significantly lower in mice colonized with choline-consuming microorganisms. Metabolites derived from other heavy methyl-consuming pathways such as purine metabolism (inosine, hypoxanthine, xanthine, kynurenine, and uric acid) and the trans-sulfuration pathway (cysteine and glutathione) were also significantly reduced. Therefore, this simple association study with a simplified microbiota demonstrated that gut bacterial metabolism significantly affects choline bioavailability for the host. In order to explore the impact of microbial choline metabolism on host energy metabolism, Romano et al. (2017) also challenged the mice colonized by CC+ and CC with a high-fat diet (HF) contain-
ing 42% Kcal fat supplemented with 1% choline for 8 weeks. Although no differences in body weight were observed, the animals colonized with the CC+ community developed increased inguinal fat storage, elevated circulating levels of leptin and of non-esterified fatty acids, consistent with the known action of leptin to stimulate lipolysis. Interestingly, this was associated with lower levels of DNA methylation in the brain, heart, liver, and colon, which suggests a state of moderate methyl donor deficiency. Methyl donor deficiencies can produce epigenetic modifications and trigger metabolic diseases (Barres and Zierath, 2011; Pogribny and Beland, 2009). Hence, these new findings contribute to the understanding of microbial choline demand, indicating that a lack of choline resources stimulates adipogenesis and may promote altered epigenetic metabolism.
254 Cell Host & Microbe 22, September 13, 2017
This observation of the impact of CC+ colonization on the epigenetic profile prompted Romano et al. (2017) to investigate the significance of these effects on fetal development because of the crucial role played by methyl donors on cell proliferation and neural tube formation during gestation (Zeisel, 2006). Female mice colonized with either CC+ or CC were maintained on a 1% choline diet for 4 weeks before mating, and full-term pups were collected by C-section. Consistent with high microbial choline degradation, TMAO was increased in plasma from CC+ mothers and was found in higher levels in their pups’ livers. Moreover, a significant reduction in DNA methylation was measured in the brain and liver of pups born from CC+ mothers. Therefore, the authors hypothesized that maternal methyl donor availability, DNA methylation profiles, and neonates’ epigenetic condition
Cell Host & Microbe
Previews are influenced by gut microbiota utilization of choline. As it is known that this can influence cognitive decline later in life, Romano and colleagues (2017) exposed ApoE / mice, used here as a model of altered cognitive skills and behavior, to cholineconsuming gut microbiota during gestation and after birth. Parents colonized with CC+ showed high levels of infanticide and barbering behaviors and their offspring also exhibited higher anxious behaviors compared to those born from CC parents. Altogether this indicates that a moderate state of methyl-donor deficiency induced by choline-consuming gut microbiota affects the behavior of both parents and their offspring. This remarkable proof of concept study—using a germ-free mouse model associated with a simplified microbiota comprised of only a total of six bacterial species—will have considerable influence on the nutrition field, if the findings are confirmed in the context of a complex microbiota. These effects must therefore be further evaluated at the level of a complex microbial ecosystem and consider the highly variable nature of human gut microbiota and host genetic polymor-
phism. Nevertheless, this original study provides evidence of a competition between choline-utilizing gut bacteria and the host that has the potential to significantly influence the bioavailability of methyl-donor compounds at a systemic level. As a consequence of this competition, epigenetic regulations may be affected and high-choline-consuming gut microbiota may predispose host animals for developing some metabolic disorders. These findings therefore represent an important step toward the development of personalized diets, where host-nutrient-gut microbiota interactions can be taken into account, so as to provide more appropriate nutritional guidelines to improve human health. In particular, population groups vulnerable to choline deficiency, such as pregnant women, may benefit tremendously from improved diet recommendations based on an individual assessment of their metabolism. ACKNOWLEDGMENTS
Commission (FP7-613979), and the Biotechnology and Biological Sciences Research Council (BB/ N021800/1). S.P.C. acts as Chief Scientific Officer for LNC Therapeutics.
REFERENCES Baker, J.R., and Chaykin, S. (1962). J. Biol. Chem. 237, 1309–1313. Barres, R., and Zierath, J.R. (2011). Am. J. Clin. Nutr. 93, 897S–900. Lang, D.H., Yeung, C.K., Peter, R.M., Ibarra, C., Gasser, R., Itagaki, K., Philpot, R.M., and Rettie, A.E. (1998). Biochem. Pharmacol. 56, 1005–1012. Lombardi, B., Pani, P., and Schlunk, F.F. (1968). J. Lipid Res. 9, 437–446. Pogribny, I.P., and Beland, F.A. (2009). Cell. Mol. Life Sci. 66, 2249–2261. Romano, K.A., Martı´nez-Del Campo, A., Kasahara, K., Chittim, C.L., Vivas, E.I., Amador-Noguez, D., Balskus, E.P., and Rey, F.E. (2017). Cell Host Microbe 22, this issue, 279–290. Winter, S.E., Winter, M.G., Xavier, M.N., Thiennimitr, P., Poon, V., Keestra, A.M., Laughlin, R.C., Gomez, G., Wu, J., Lawhon, S.D., et al. (2013). Science 339, 708–711. Zeisel, S.H. (2000). Nutrition 16, 669–671.
S.P.C. is the recipient of funding by the Medical Research Council (MR/M004945/1), the European
Zeisel, S.H. (2006). Annu. Rev. Nutr. 26, 229–250.
Fragment and Conquer Vera Kozjak-Pavlovic,1 Suvagata Roy Chowdhury,1 and Thomas Rudel1,* 1Department of Microbiology, Biocenter, University of Wuerzburg, Am Hubland, D-97074 Wuerzburg, Germany *Correspondence: [email protected] http://dx.doi.org/10.1016/j.chom.2017.08.014
The replication vacuole of Legionella pneumophila makes contact with host mitochondria. In this issue of Cell Host & Microbe, Escoll et al. (2017) dissect the mechanisms of this interaction, the effect of the T4SS effector MitF on mitochondrial function, and the resultant metabolic reprogramming of infected cells to benefit the bacteria. Intracellular bacterial pathogens such as Legionella are invariably dependent on the metabolic and bioenergetic status of the host cell. The host mitochondrial network is one of the key players in the maintenance of bioenergetics and physiological homeostasis within the eukaryotic cell. The mitochondrial network and its effect on cellular health, however, are not defined entirely by the ATP production
that is so often discussed. The mitochondrial network is incessantly dynamic as a result of constant fusion and fission of mitochondrial fragments, which are tightly governed by a plethora of cytoplasmic and mitochondrial proteins. While the movements of the mitochondrial fragments appear random, recent studies and reviews on the mitochondrial network illustrate that the fine-tuned nature of mito-
chondrial motility and architecture affect and are affected by cellular bioenergetics, metabolism, survival, stress, and disease conditions. Previous studies have demonstrated how certain bacterial pathogens affect mitochondrial function by targeting proteins regulating mitochondrial fission (Chowdhury et al., 2017; Jain et al., 2011; Lum and Morona, 2014). In this preview, we shine the spotlight on findings by Escoll
Cell Host & Microbe 22, September 13, 2017 ª 2017 Elsevier Inc. 255
Previews Gomez, A., Espinoza, J.L., Harkins, D.M., Leong, P., Saffery, R., Bockmann, M., Tarralba, M., Kuelbs, C., Kodukula, R., Inman, J., et al. (2017). Cell Host Microbe 22, this issue, 269–278. Goodrich, J.K., Davenport, E.R., Waters, J.L., Clark, A.G., and Ley, R.E. (2016). Science 352, 532–535.
Kavanagh, K., and Dowd, S. (2004). J. Pharm. Pharmacol. 56, 285–289. Mark Welch, J.L., Rossetti, B.J., Rieken, C.W., Dewhirst, F.E., and Borisy, G.G. (2016). Proc. Natl. Acad. Sci. USA 113, E791–E800. Oppenheim, F.G., Salih, E., Siqueira, W.L., Zhang, W., and Helmerhorst, E.J. (2007). Ann. N Y Acad. Sci. 1098, 22–50.
Perry, G.H., Dominy, N.J., Claw, K.G., Lee, A.S., Fiegler, H., Redon, R., Werner, J., Villanea, F.A., Mountain, J.L., Misra, R., et al. (2007). Nat. Genet. 39, 1256–1260. Xu, D., Pavlidis, P., Taskent, R.O., Alachiotis, N., Flanagan, C., DeGiorgio, M., Blekhman, R., Ruhl, S., and Gokcumen, O. (2017). Mol. Biol. Evol. Published online July 21, 2017. http://dx.doi.org/10. 1093/molbev/msx206.
Choline Theft—An Inside Job Marina Mora-Ortiz1 and Sandrine Paule Claus1,* 1Department of Food and Nutritional Sciences, University of Reading, Whiteknights Campus, PO Box 226, Reading RG6 6AP, UK *Correspondence: [email protected] http://dx.doi.org/10.1016/j.chom.2017.08.017
Choline is a crucial methyl donor necessary for epigenetic regulation. In this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline-utilizing gut bacteria compete with their host for this essential resource, calling for a systematic consideration of gut microbial composition for personalized diet recommendations.
Choline is an essential nutrient abundant in diet, especially in high-protein-containing food such as eggs, red meat, soy beans, and wheat germs. It is critical for neurotransmission (as it is the precursor of the neurotransmitter acetylcholine), for epigenetic regulation via the synthesis of the major methyl donor S-adenosylmethionine (SAM), and is necessary to produce phosphatidylcholine, the ubiquitous phospholipid that ensures the integrity of cell membranes (Zeisel, 2000). Choline’s essential nature has been widely evidenced by studies in which choline deficiency results in abnormalities in epigenetic regulation and lipid metabolism (Lombardi et al., 1968; Pogribny and Beland, 2009). Following ingestion, some dietary choline is transformed by the gut microbial enzyme, choline trimethylamine (TMA) lyase, into TMA and acetaldehyde. TMA is then absorbed through the portal blood system and reaches the liver, where it is oxidized into trimethylamineN-oxide (TMAO) by the host flavin monooxygenase 3 (FMO3) (Baker and Chaykin, 1962; Lang et al., 1998) (Figure 1). In an elegant investigation published in this issue of Cell Host & Microbe, Romano et al. (2017) demonstrate that choline metabolism by gut bacteria plays a signif-
icant role in modulating host access to this resource (Romano et al., 2017). They first identified a choline-utilization gene cluster, cut, in a strain of E. coli (MS 200-1) isolated from the ileum of a healthy human donor. They show that this ‘‘type II’’ cut gene cluster encodes all the proteins required for anaerobic choline metabolism, including CutC and CutD, the choline-TMA lyase and its activase, respectively. Inspection of the genetic context of the cut gene cluster in g-Proteobacteria (of which E. coli is a member) allowed them to identify other genes potentially linked to choline usage absent in the type I cut cluster, which is abundant in Firmicutes, Actinobacteria, and d-Proteobacteria. Romano et al. (2017) then confirmed the role of the E. coli cut gene cluster in choline metabolism by knocking out cutC and cutD. These mutants were unable to grow on a restricted medium containing choline as the sole carbon source and failed to convert choline into TMA, demonstrating their essential involvement in TMA production from dietary choline. Next, they determined that the respiratory electron acceptors fumarate, nitrate, DMSO, and TMAO supported bacterial growth on choline as a carbon source in anaerobic conditions.
Given that nitrate is known to be released into the lumen during gut inflammation and that some E. coli sp. use it as an electron acceptor during anaerobic growth, Romano et al. (2017) hypothesized that the bacterial strains able to couple nitrate respiration with choline usage could bear an evolutionary advantage in the inflamed gut as previously suggested (Winter et al., 2013). Romano et al. (2017) further hypothesized that choline-consuming bacteria may have a significant impact on host choline-utilization pathways. To test this hypothesis, they developed a gnotobiotic model consisting of adult germ-free mice associated with a simplified gut microbiota composed of five bacteria common in the human gut that are unable to metabolize choline and added either a wild-type choline-consuming E. coli (CC+) or a cutC knockout (DcutC) non-choline consuming mutant strain (CC ). Deletion of the cutC gene significantly impaired E. coli colonization, suggesting that cholineconsuming E. coli receive a fitness advantage in vivo and that choline metabolism modulates the composition of gut bacterial communities. Importantly, CC+ colonization resulted in an altered host plasma metabolome, in which circulating levels
Cell Host & Microbe 22, September 13, 2017 ª 2017 Published by Elsevier Inc. 253
Cell Host & Microbe
Previews
Figure 1. Host-Gut Microbiota Co-metabolism of Choline Most of the daily intake of choline is readily absorbed in the upper-gastrointestinal tract. From there it is used directly by the liver as a methyl donor into the methylation pathway, which contributes to the endogenous synthesis of trimethylamine (TMA) and trimethylamine-N-oxide (TMAO). Unabsorbed dietary choline can also be metabolized by gut bacteria into TMA by TMA-lyase, which is encoded by the bacterial cut gene cluster. Some gut bacteria can oxidize TMA into TMAO, both of which can also be degraded into dimethylamine (DMA), methylamine (MA), and ammonia (NH3). Alternatively, TMA can be absorbed by the portal blood system and be further oxidized into TMAO by the hepatic flavin monooxygenase 3 enzyme. SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; THF, tetrahydrofolic acid; BHMT, betaine homocysteine S-methyltransferase; FC, folate cycle.
of metabolites involved in the methylation pathway (i.e., choline, betaine, methionine, dimethylglycine, and methionine sulfoxide), and therefore in the production of SAM, were significantly lower in mice colonized with choline-consuming microorganisms. Metabolites derived from other heavy methyl-consuming pathways such as purine metabolism (inosine, hypoxanthine, xanthine, kynurenine, and uric acid) and the trans-sulfuration pathway (cysteine and glutathione) were also significantly reduced. Therefore, this simple association study with a simplified microbiota demonstrated that gut bacterial metabolism significantly affects choline bioavailability for the host. In order to explore the impact of microbial choline metabolism on host energy metabolism, Romano et al. (2017) also challenged the mice colonized by CC+ and CC with a high-fat diet (HF) contain-
ing 42% Kcal fat supplemented with 1% choline for 8 weeks. Although no differences in body weight were observed, the animals colonized with the CC+ community developed increased inguinal fat storage, elevated circulating levels of leptin and of non-esterified fatty acids, consistent with the known action of leptin to stimulate lipolysis. Interestingly, this was associated with lower levels of DNA methylation in the brain, heart, liver, and colon, which suggests a state of moderate methyl donor deficiency. Methyl donor deficiencies can produce epigenetic modifications and trigger metabolic diseases (Barres and Zierath, 2011; Pogribny and Beland, 2009). Hence, these new findings contribute to the understanding of microbial choline demand, indicating that a lack of choline resources stimulates adipogenesis and may promote altered epigenetic metabolism.
254 Cell Host & Microbe 22, September 13, 2017
This observation of the impact of CC+ colonization on the epigenetic profile prompted Romano et al. (2017) to investigate the significance of these effects on fetal development because of the crucial role played by methyl donors on cell proliferation and neural tube formation during gestation (Zeisel, 2006). Female mice colonized with either CC+ or CC were maintained on a 1% choline diet for 4 weeks before mating, and full-term pups were collected by C-section. Consistent with high microbial choline degradation, TMAO was increased in plasma from CC+ mothers and was found in higher levels in their pups’ livers. Moreover, a significant reduction in DNA methylation was measured in the brain and liver of pups born from CC+ mothers. Therefore, the authors hypothesized that maternal methyl donor availability, DNA methylation profiles, and neonates’ epigenetic condition
Cell Host & Microbe
Previews are influenced by gut microbiota utilization of choline. As it is known that this can influence cognitive decline later in life, Romano and colleagues (2017) exposed ApoE / mice, used here as a model of altered cognitive skills and behavior, to cholineconsuming gut microbiota during gestation and after birth. Parents colonized with CC+ showed high levels of infanticide and barbering behaviors and their offspring also exhibited higher anxious behaviors compared to those born from CC parents. Altogether this indicates that a moderate state of methyl-donor deficiency induced by choline-consuming gut microbiota affects the behavior of both parents and their offspring. This remarkable proof of concept study—using a germ-free mouse model associated with a simplified microbiota comprised of only a total of six bacterial species—will have considerable influence on the nutrition field, if the findings are confirmed in the context of a complex microbiota. These effects must therefore be further evaluated at the level of a complex microbial ecosystem and consider the highly variable nature of human gut microbiota and host genetic polymor-
phism. Nevertheless, this original study provides evidence of a competition between choline-utilizing gut bacteria and the host that has the potential to significantly influence the bioavailability of methyl-donor compounds at a systemic level. As a consequence of this competition, epigenetic regulations may be affected and high-choline-consuming gut microbiota may predispose host animals for developing some metabolic disorders. These findings therefore represent an important step toward the development of personalized diets, where host-nutrient-gut microbiota interactions can be taken into account, so as to provide more appropriate nutritional guidelines to improve human health. In particular, population groups vulnerable to choline deficiency, such as pregnant women, may benefit tremendously from improved diet recommendations based on an individual assessment of their metabolism. ACKNOWLEDGMENTS
Commission (FP7-613979), and the Biotechnology and Biological Sciences Research Council (BB/ N021800/1). S.P.C. acts as Chief Scientific Officer for LNC Therapeutics.
REFERENCES Baker, J.R., and Chaykin, S. (1962). J. Biol. Chem. 237, 1309–1313. Barres, R., and Zierath, J.R. (2011). Am. J. Clin. Nutr. 93, 897S–900. Lang, D.H., Yeung, C.K., Peter, R.M., Ibarra, C., Gasser, R., Itagaki, K., Philpot, R.M., and Rettie, A.E. (1998). Biochem. Pharmacol. 56, 1005–1012. Lombardi, B., Pani, P., and Schlunk, F.F. (1968). J. Lipid Res. 9, 437–446. Pogribny, I.P., and Beland, F.A. (2009). Cell. Mol. Life Sci. 66, 2249–2261. Romano, K.A., Martı´nez-Del Campo, A., Kasahara, K., Chittim, C.L., Vivas, E.I., Amador-Noguez, D., Balskus, E.P., and Rey, F.E. (2017). Cell Host Microbe 22, this issue, 279–290. Winter, S.E., Winter, M.G., Xavier, M.N., Thiennimitr, P., Poon, V., Keestra, A.M., Laughlin, R.C., Gomez, G., Wu, J., Lawhon, S.D., et al. (2013). Science 339, 708–711. Zeisel, S.H. (2000). Nutrition 16, 669–671.
S.P.C. is the recipient of funding by the Medical Research Council (MR/M004945/1), the European
Zeisel, S.H. (2006). Annu. Rev. Nutr. 26, 229–250.
Fragment and Conquer Vera Kozjak-Pavlovic,1 Suvagata Roy Chowdhury,1 and Thomas Rudel1,* 1Department of Microbiology, Biocenter, University of Wuerzburg, Am Hubland, D-97074 Wuerzburg, Germany *Correspondence: [email protected] http://dx.doi.org/10.1016/j.chom.2017.08.014
The replication vacuole of Legionella pneumophila makes contact with host mitochondria. In this issue of Cell Host & Microbe, Escoll et al. (2017) dissect the mechanisms of this interaction, the effect of the T4SS effector MitF on mitochondrial function, and the resultant metabolic reprogramming of infected cells to benefit the bacteria. Intracellular bacterial pathogens such as Legionella are invariably dependent on the metabolic and bioenergetic status of the host cell. The host mitochondrial network is one of the key players in the maintenance of bioenergetics and physiological homeostasis within the eukaryotic cell. The mitochondrial network and its effect on cellular health, however, are not defined entirely by the ATP production
that is so often discussed. The mitochondrial network is incessantly dynamic as a result of constant fusion and fission of mitochondrial fragments, which are tightly governed by a plethora of cytoplasmic and mitochondrial proteins. While the movements of the mitochondrial fragments appear random, recent studies and reviews on the mitochondrial network illustrate that the fine-tuned nature of mito-
chondrial motility and architecture affect and are affected by cellular bioenergetics, metabolism, survival, stress, and disease conditions. Previous studies have demonstrated how certain bacterial pathogens affect mitochondrial function by targeting proteins regulating mitochondrial fission (Chowdhury et al., 2017; Jain et al., 2011; Lum and Morona, 2014). In this preview, we shine the spotlight on findings by Escoll
Cell Host & Microbe 22, September 13, 2017 ª 2017 Elsevier Inc. 255