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Mitochondrial potassium channels: Magnum overview
Biochimica et Biophysica Acta 1817 (2012) S83–S89
Contents lists available at SciVerse ScienceDirect
Biochimica et Biophysica Acta j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / b b a b i o
S11 Signaling 11L1 Signalling pathways regulating mitochondrial protein import Chris Meisinger Institute of Biochemistry and Molecularbiology and BIOSS (Centre for Biological Signalling Studies), Freiburg University, Germany E-mail: [email protected] Analysis of the mitochondrial proteome of S. cerevisiae led to the identification of 851 different proteins. This dataset covers approx. 85% of the proteome. More than 200 proteins were of unknown function. Some of these were identified as components of novel protein import pathways, such as the sorting and assembly machinery (SAM-complex) in the outer membrane and the MIA machinery in the intermembrane space. A surprising finding was the presence of many signaling proteins including protein kinases, phosphatases and G-proteins. Further systematic analysis revealed a substantial fraction of phosphorylated mitochondrial proteins indicating a role of reversible phosphorylation in regulating mitochondrial function. A remarkable high number of phosphorylation sites were identified in outer membrane proteins particularly in components regulating mitochondrial biogenesis. We have identified several protein kinases which phosphorylate these proteins and analyzed how protein import and assembly are embedded in a cellular signalling network. References [1] C. Meisinger, A. Sickmann, N. Pfanner, The mitochondrial proteome: from inventory to function, Cell 134 (2008) 22–24. [2] O. Schmidt, N. Pfanner, C. Meisinger, Mitochondrial protein import: from proteomics to functional mechanisms, Nature Rev. Mol. Cell. Biol. 11 (2010) 655–667. [3] O. Schmidt, A.B. Harbauer, S. Rao, B. Eyrich, R.P. Zahedi, D. Stojanovski, B. Schönfisch, B. Guiard, A. Sickmann, N. Pfanner, C. Meisinger, Regulation of mitochondrial protein import by cytosolic kinases, Cell 144 (2011) 227–239. [4] S. Rao, C. Gerbeth, A. Harbauer, D. Mikropoulou, C. Meisinger, O. Schmidt, Signaling at the gate: phosphorylation of the mitochondrial protein import machinery, Cell Cycle 10 (2011) 2083–2090. doi:10.1016/j.bbabio.2012.06.225
11L2 Mitochondrial potassium channels: Magnum overview A. Szewczyk Nencki Institute of Experimental Biology, Laboratory of Intracellular Ion Channels, Pasteura 3, PL-02-093 Warsaw, Poland E-mail: [email protected] 0005-2728/$ – see front matter.
Mitochondrial potassium channels play an important role in cytoprotection. The following potassium channels have been described in the inner mitochondrial membrane: the ATP-regulated potassium channel, the large conductance calcium activated potassium channel, the voltage-gated potassium channel and the twin-pore domain TASK-3 potassium channel. Potassium channels in the inner mitochondrial membrane are modulated by inhibitors and activators (potassium channel openers) previously described for plasma membrane potassium channels. The majority of mitochondrial potassium channel modulators exhibit a broad spectrum of off-target effects. These include uncoupling properties, inhibition of the respiratory chain and effects on cellular calcium homeostasis. Therefore, the rational application of channel inhibitors or activators is crucial to understanding the cellular consequences of mitochondrial channel inhibition or activation. In this paper, recent observations on three fundamental issues concerning mitochondrial potassium channel will be discussed: 1). their molecular identity, 2). their interaction with potassium channel openers and inhibitors and 3). their functional role. This study was supported by the European Union from the resources of the European Regional Development Fund under the Innovative Economy Programme (POIG.01.01.02-00-069/09). doi:10.1016/j.bbabio.2012.06.226
11P1 New insights into interactions of hemin and calcium-regulated BK channel in rat brain mitochondria B. Augustynek1,3, P. Bednarczyk2, W.S. Kunz3, A. Szewczyk1 1 Nencki Institute of Experimental Biology, Laboratory of Intracellular Ion Channels, Pasteura 3, PL-02-093 Warsaw, Poland 2 Warsaw University of Life Sciences, Department of Biophysics, Nowoursynowska 159, PL-02-776 Warszawa, Poland 3 Department of Epileptology, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany E-mail: [email protected] Heme is a prosthetic group that consists of an iron atom bound in the center of a porphyrin ring. It is an essential element of hemeproteins in all living organisms. Although heme is ubiquitous, its circulation is strictly controlled. Therefore it is believed that it may play as yet unknown regulatory functions. The mitochondrial calcium-dependent BK channel (mitoBKCa) is one of the five known channels that contribute to potassium permeability of mitochondrial inner membrane. It is activated by calcium and voltage and inhibited by scorpion venom toxins such as charybdotoxin and iberiotoxin.
Contents lists available at SciVerse ScienceDirect
Biochimica et Biophysica Acta j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / b b a b i o
S11 Signaling 11L1 Signalling pathways regulating mitochondrial protein import Chris Meisinger Institute of Biochemistry and Molecularbiology and BIOSS (Centre for Biological Signalling Studies), Freiburg University, Germany E-mail: [email protected] Analysis of the mitochondrial proteome of S. cerevisiae led to the identification of 851 different proteins. This dataset covers approx. 85% of the proteome. More than 200 proteins were of unknown function. Some of these were identified as components of novel protein import pathways, such as the sorting and assembly machinery (SAM-complex) in the outer membrane and the MIA machinery in the intermembrane space. A surprising finding was the presence of many signaling proteins including protein kinases, phosphatases and G-proteins. Further systematic analysis revealed a substantial fraction of phosphorylated mitochondrial proteins indicating a role of reversible phosphorylation in regulating mitochondrial function. A remarkable high number of phosphorylation sites were identified in outer membrane proteins particularly in components regulating mitochondrial biogenesis. We have identified several protein kinases which phosphorylate these proteins and analyzed how protein import and assembly are embedded in a cellular signalling network. References [1] C. Meisinger, A. Sickmann, N. Pfanner, The mitochondrial proteome: from inventory to function, Cell 134 (2008) 22–24. [2] O. Schmidt, N. Pfanner, C. Meisinger, Mitochondrial protein import: from proteomics to functional mechanisms, Nature Rev. Mol. Cell. Biol. 11 (2010) 655–667. [3] O. Schmidt, A.B. Harbauer, S. Rao, B. Eyrich, R.P. Zahedi, D. Stojanovski, B. Schönfisch, B. Guiard, A. Sickmann, N. Pfanner, C. Meisinger, Regulation of mitochondrial protein import by cytosolic kinases, Cell 144 (2011) 227–239. [4] S. Rao, C. Gerbeth, A. Harbauer, D. Mikropoulou, C. Meisinger, O. Schmidt, Signaling at the gate: phosphorylation of the mitochondrial protein import machinery, Cell Cycle 10 (2011) 2083–2090. doi:10.1016/j.bbabio.2012.06.225
11L2 Mitochondrial potassium channels: Magnum overview A. Szewczyk Nencki Institute of Experimental Biology, Laboratory of Intracellular Ion Channels, Pasteura 3, PL-02-093 Warsaw, Poland E-mail: [email protected] 0005-2728/$ – see front matter.
Mitochondrial potassium channels play an important role in cytoprotection. The following potassium channels have been described in the inner mitochondrial membrane: the ATP-regulated potassium channel, the large conductance calcium activated potassium channel, the voltage-gated potassium channel and the twin-pore domain TASK-3 potassium channel. Potassium channels in the inner mitochondrial membrane are modulated by inhibitors and activators (potassium channel openers) previously described for plasma membrane potassium channels. The majority of mitochondrial potassium channel modulators exhibit a broad spectrum of off-target effects. These include uncoupling properties, inhibition of the respiratory chain and effects on cellular calcium homeostasis. Therefore, the rational application of channel inhibitors or activators is crucial to understanding the cellular consequences of mitochondrial channel inhibition or activation. In this paper, recent observations on three fundamental issues concerning mitochondrial potassium channel will be discussed: 1). their molecular identity, 2). their interaction with potassium channel openers and inhibitors and 3). their functional role. This study was supported by the European Union from the resources of the European Regional Development Fund under the Innovative Economy Programme (POIG.01.01.02-00-069/09). doi:10.1016/j.bbabio.2012.06.226
11P1 New insights into interactions of hemin and calcium-regulated BK channel in rat brain mitochondria B. Augustynek1,3, P. Bednarczyk2, W.S. Kunz3, A. Szewczyk1 1 Nencki Institute of Experimental Biology, Laboratory of Intracellular Ion Channels, Pasteura 3, PL-02-093 Warsaw, Poland 2 Warsaw University of Life Sciences, Department of Biophysics, Nowoursynowska 159, PL-02-776 Warszawa, Poland 3 Department of Epileptology, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany E-mail: [email protected] Heme is a prosthetic group that consists of an iron atom bound in the center of a porphyrin ring. It is an essential element of hemeproteins in all living organisms. Although heme is ubiquitous, its circulation is strictly controlled. Therefore it is believed that it may play as yet unknown regulatory functions. The mitochondrial calcium-dependent BK channel (mitoBKCa) is one of the five known channels that contribute to potassium permeability of mitochondrial inner membrane. It is activated by calcium and voltage and inhibited by scorpion venom toxins such as charybdotoxin and iberiotoxin.