Mitochondrial Glutathione: Regulation and Functions
Publication: Antioxidants & Redox Signaling
Volume 27, Issue Number 15
Abstract
Significance: Mitochondrial glutathione fulfills crucial roles in a number of processes, including iron–sulfur cluster biosynthesis and peroxide detoxification.
Recent Advances: Genetically encoded fluorescent probes for the glutathione redox potential (EGSH) have permitted extensive new insights into the regulation of mitochondrial glutathione redox homeostasis. These probes have revealed that the glutathione pools of the mitochondrial matrix and intermembrane space (IMS) are highly reduced, similar to the cytosolic glutathione pool. The glutathione pool of the IMS is in equilibrium with the cytosolic glutathione pool due to the presence of porins that allow free passage of reduced glutathione (GSH) and oxidized glutathione (GSSG) across the outer mitochondrial membrane. In contrast, limited transport of glutathione across the inner mitochondrial membrane ensures that the matrix glutathione pool is kinetically isolated from the cytosol and IMS.
Critical Issues: In contrast to the situation in the cytosol, there appears to be extensive crosstalk between the mitochondrial glutathione and thioredoxin systems. Further, both systems appear to be intimately involved in the removal of reactive oxygen species, particularly hydrogen peroxide (H2O2), produced in mitochondria. However, a detailed understanding of these interactions remains elusive.
Future Directions: We postulate that the application of genetically encoded sensors for glutathione in combination with novel H2O2 probes and conventional biochemical redox state assays will lead to fundamental new insights into mitochondrial redox regulation and reinvigorate research into the physiological relevance of mitochondrial redox changes. Antioxid. Redox Signal. 27, 1162–1177.
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References
1.
Allen S, Balabanidou V, Sideris DP, Lisowsky T, and Tokatlidis K. Erv1 mediates the Mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c. J Mol Biol 353: 937–944, 2005.
2.
Applegate MA, Humphries KM, and Szweda LI. Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide: glutathionylation and protection of lipoic acid. Biochemistry 47: 473–478, 2008.
3.
Avery AM and Avery SV. Saccharomyces cerevisiae expresses three phospholipid hydroperoxide glutathione peroxidases. J Biol Chem 276: 33730–33735, 2001.
4.
Avery AM, Willetts SA, and Avery SV. Genetic dissection of the phospholipid hydroperoxidase activity of yeast gpx3 reveals its functional importance. J Biol Chem 279: 46652–46658, 2004.
5.
Ayer A, Fellermeier S, Fife C, Li SS, Smits G, Meyer AJ, Dawes IW, and Perrone GG. A genome-wide screen in yeast identifies specific oxidative stress genes required for the maintenance of sub-cellular redox homeostasis. PLoS One 7: e44278, 2012.
6.
Ayer A, Sanwald J, Pillay BA, Meyer AJ, Perrone GG, and Dawes IW. Distinct redox regulation in sub-cellular compartments in response to various stress conditions in Saccharomyces cerevisiae. PLoS One 8: e65240, 2013.
7.
Ayer A, Tan SX, Grant CM, Meyer AJ, Dawes IW, and Perrone GG. The critical role of glutathione in maintenance of the mitochondrial genome. Free Radic Biol Med 49: 1956–1968, 2010.
8.
Ballatori N, Hammond CL, Cunningham JB, Krance SM, and Marchan R. Molecular mechanisms of reduced glutathione transport: role of the MRP/CFTR/ABCC and OATP/SLC21A families of membrane proteins. Toxicol Appl Pharmacol 204: 238–255, 2005.
9.
Ballatori N, Krance SM, Marchan R, and Hammond CL. Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology. Mol Aspects Med 30: 13–28, 2009.
10.
Banci L, Brancaccio D, Ciofi-Baffoni S, Del Conte R, Gadepalli R, Mikolajczyk M, Neri S, Piccioli M, and Winkelmann J. [2Fe-2S] cluster transfer in iron-sulfur protein biogenesis. Proc Natl Acad Sci U S A 111: 6203–6208, 2014.
11.
Bandyopadhyay S, Gama F, Molina-Navarro MM, Gualberto JM, Claxton R, Naik SG, Huynh BH, Herrero E, Jacquot JP, Johnson MK, and Rouhier N. Chloroplast monothiol glutaredoxins as scaffold proteins for the assembly and delivery of [2Fe-2S] clusters. EMBO J 27: 1122–1133, 2008.
12.
Barbot M, Jans DC, Schulz C, Denkert N, Kroppen B, Hoppert M, Jakobs S, and Meinecke M. Mic10 oligomerizes to bend mitochondrial inner membranes at cristae junctions. Cell Metab 21: 756–763, 2015.
13.
Becker T, Gebert M, Pfanner N, and van der Laan M. Biogenesis of mitochondrial membrane proteins. Curr Opin Cell Biol 21: 484–493, 2009.
14.
Bien M, Longen S, Wagener N, Chwalla I, Herrmann JM, and Riemer J. Mitochondrial disulfide bond formation is driven by intersubunit electron transfer in Erv1 and proofread by glutathione. Mol Cell 37: 516–528, 2010.
15.
Birk J, Meyer M, Aller I, Hansen HG, Odermatt A, Dick TP, Meyer AJ, and Appenzeller-Herzog C. Endoplasmic reticulum: reduced and oxidized glutathione revisited. J Cell Sci 126: 1604–1617, 2013.
16.
Booty LM, King MS, Thangaratnarajah C, Majd H, James AM, Kunji ER, and Murphy MP. The mitochondrial dicarboxylate and 2-oxoglutarate carriers do not transport glutathione. FEBS Lett 589: 621–628, 2015.
17.
Carbonera D and Azzone GF. Permeability of inner mitochondrial membrane and oxidative stress. Biochim Biophys Acta 943: 245–255, 1988.
18.
Chacinska A, Koehler CM, Milenkovic D, Lithgow T, and Pfanner N. Importing mitochondrial proteins: machineries and mechanisms. Cell 138: 628–644, 2009.
19.
Chae HZ, Chung SJ, and Rhee SG. Thioredoxin-dependent peroxide reductase from yeast. J Biol Chem 269: 27670–27678, 1994.
20.
Chen YR, Chen CL, Pfeiffer DR, and Zweier JL. Mitochondrial complex II in the post-ischemic heart: oxidative injury and the role of protein S-glutathionylation. J Biol Chem 282: 32640–32654, 2007.
21.
Chen Z and Lash LH. Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers. J Pharmacol Exp Ther 285: 608–618, 1998.
22.
Chen Z, Putt DA, and Lash LH. Enrichment and functional reconstitution of glutathione transport activity from rabbit kidney mitochondria: further evidence for the role of the dicarboxylate and 2-oxoglutarate carriers in mitochondrial glutathione transport. Arch Biochem Biophys 373: 193–202, 2000.
23.
Cogliati S, Enriquez JA, and Scorrano L. Mitochondrial cristae: where beauty meets functionality. Trends Biochem Sci 41: 261–273, 2016.
24.
Collinson EJ and Grant CM. Role of yeast glutaredoxins as glutathione S-transferases. J Biol Chem 278: 22492–22497, 2003.
25.
Cummings BS, Angeles R, McCauley RB, and Lash LH. Role of voltage-dependent anion channels in glutathione transport into yeast mitochondria. Biochem Biophys Res Commun 276: 940–944, 2000.
26.
Dardalhon M, Kumar C, Iraqui I, Vernis L, Kienda G, Banach-Latapy A, He T, Chanet R, Faye G, Outten CE, and Huang ME. Redox-sensitive YFP sensors monitor dynamic nuclear and cytosolic glutathione redox changes. Free Radic Biol Med 52: 2254–2265, 2012.
27.
Deponte M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 1830: 3217–3266, 2013.
28.
Deponte M and Hell K. Disulphide bond formation in the intermembrane space of mitochondria. J Biochem 146: 599–608, 2009.
29.
Endo T and Yamano K. Multiple pathways for mitochondrial protein traffic. Biol Chem 390: 723–730, 2009.
30.
Ezerina D, Morgan B, and Dick TP. Imaging dynamic redox processes with genetically encoded probes. J Mol Cell Cardiol 73: 43–49, 2014.
31.
Fan J, Ye J, Kamphorst JJ, Shlomi T, Thompson CB, and Rabinowitz JD. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 510: 298–302, 2014.
32.
Filipovska A and Murphy MP. Measurement of protein glutathionylation. Curr Protoc Toxicol Chapter 6: Unit6 11, 2006.
33.
Fischer M, Horn S, Belkacemi A, Kojer K, Petrungaro C, Habich M, Ali M, Kuttner V, Bien M, Kauff F, Dengjel J, Herrmann JM, and Riemer J. Protein import and oxidative folding in the mitochondrial intermembrane space of intact mammalian cells. Mol Biol Cell 24: 2160–2170, 2013.
34.
Flohe L. The fairytale of the GSSG/GSH redox potential. Biochim Biophys Acta 1830: 3139–3142, 2013.
35.
Ganguli D, Kumar C, and Bachhawat AK. The alternative pathway of glutathione degradation is mediated by a novel protein complex involving three new genes in Saccharomyces cerevisiae. Genetics 175: 1137–1151, 2007.
36.
Garcera A, Barreto L, Piedrafita L, Tamarit J, and Herrero E. Saccharomyces cerevisiae cells have three omega class glutathione S-transferases acting as 1-Cys thiol transferases. Biochem J 398: 187–196, 2006.
37.
Garcia J, Han D, Sancheti H, Yap LP, Kaplowitz N, and Cadenas E. Regulation of mitochondrial glutathione redox status and protein glutathionylation by respiratory substrates. J Biol Chem 285: 39646–39654, 2010.
38.
Gaudet P, Livstone MS, Lewis SE, and Thomas PD. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief Bioinform 12: 449–462, 2011.
39.
Gostimskaya I and Grant CM. Yeast mitochondrial glutathione is an essential antioxidant with mitochondrial thioredoxin providing a back-up system. Free Radic Biol Med 94: 55–65, 2016.
40.
Grant CM, Collinson LP, Roe JH, and Dawes IW. Yeast glutathione reductase is required for protection against oxidative stress and is a target gene for yAP-1 transcriptional regulation. Mol Microbiol 21: 171–179, 1996.
41.
Grant CM, MacIver FH, and Dawes IW. Glutathione synthetase is dispensable for growth under both normal and oxidative stress conditions in the yeast Saccharomyces cerevisiae due to an accumulation of the dipeptide gamma-glutamylcysteine. Mol Biol Cell 8: 1699–1707, 1997.
42.
Greetham D and Grant CM. Antioxidant activity of the yeast mitochondrial one-Cys peroxiredoxin is dependent on thioredoxin reductase and glutathione in vivo. Mol Cell Biol 29: 3229–3240, 2009.
43.
Greetham D, Kritsiligkou P, Watkins RH, Carter Z, Parkin J, and Grant CM. Oxidation of the yeast mitochondrial thioredoxin promotes cell death. Antioxid Redox Signal 18: 376–385, 2013.
44.
Gutscher M, Pauleau AL, Marty L, Brach T, Wabnitz GH, Samstag Y, Meyer AJ, and Dick TP. Real-time imaging of the intracellular glutathione redox potential. Nat Methods 5: 553–559, 2008.
45.
Hackenbrock CR. Ultrastructural bases for metabolically linked mechanical activity in mitochondria. I. Reversible ultrastructural changes with change in metabolic steady state in isolated liver mitochondria. J Cell Biol 30: 269–297, 1966.
46.
Hanson GT, Aggeler R, Oglesbee D, Cannon M, Capaldi RA, Tsien RY, and Remington SJ. Investigating mitochondrial redox potential with redox-sensitive green fluorescent protein indicators. J Biol Chem 279: 13044–13053, 2004.
47.
Harner M, Korner C, Walther D, Mokranjac D, Kaesmacher J, Welsch U, Griffith J, Mann M, Reggiori F, and Neupert W. The mitochondrial contact site complex, a determinant of mitochondrial architecture. EMBO J 30: 4356–4370, 2011.
48.
Heisterkamp N, Groffen J, Warburton D, and Sneddon TP. The human gamma-glutamyltransferase gene family. Hum Genet 123: 321–332, 2008.
49.
Horvath SE, Rampelt H, Oeljeklaus S, Warscheid B, van der Laan M, and Pfanner N. Role of membrane contact sites in protein import into mitochondria. Protein Sci 24: 277–297, 2015.
50.
Hu J, Dong L, and Outten CE. The redox environment in the mitochondrial intermembrane space is maintained separately from the cytosol and matrix. J Biol Chem 283: 29126–29134, 2008.
51.
Huang CS, Anderson ME, and Meister A. Amino acid sequence and function of the light subunit of rat kidney gamma-glutamylcysteine synthetase. J Biol Chem 268: 20578–20583, 1993.
52.
Huang CS, Chang LS, Anderson ME, and Meister A. Catalytic and regulatory properties of the heavy subunit of rat kidney gamma-glutamylcysteine synthetase. J Biol Chem 268: 19675–19680, 1993.
53.
Huh WK, Falvo JV, Gerke LC, Carroll AS, Howson RW, Weissman JS, and O'Shea EK. Global analysis of protein localization in budding yeast. Nature 425: 686–691, 2003.
54.
Inoue Y, Matsuda T, Sugiyama K, Izawa S, and Kimura A. Genetic analysis of glutathione peroxidase in oxidative stress response of Saccharomyces cerevisiae. J Biol Chem 274: 27002–27009, 1999.
55.
Inoue Y, Sugiyama K, Izawa S, and Kimura A. Molecular identification of glutathione synthetase (GSH2) gene from Saccharomyces cerevisiae. Biochim Biophys Acta 1395: 315–320, 1998.
56.
Jackson JB. Proton translocation by transhydrogenase. FEBS Lett 545: 18–24, 2003.
57.
Jaspers CJ and Penninckx MJ. Glutathione metabolism in yeast Saccharomyces cerevisiae. Evidence that gamma-glutamyltranspeptidase is a vacuolar enzyme. Biochimie 66: 71–74, 1984.
58.
Jedlitschky G, Leier I, Buchholz U, Barnouin K, Kurz G, and Keppler D. Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res 56: 988–994, 1996.
59.
Jo SH, Son MK, Koh HJ, Lee SM, Song IH, Kim YO, Lee YS, Jeong KS, Kim WB, Park JW, Song BJ, and Huh TL. Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase. J Biol Chem 276: 16168–16176, 2001.
60.
Kang PT, Chen CL, and Chen YR. Increased mitochondrial prooxidant activity mediates up-regulation of Complex I S-glutathionylation via protein thiyl radical in the murine heart of eNOS(-/-). Free Radic Biol Med 79: 56–68, 2015.
61.
Kaur H, Ganguli D, and Bachhawat AK. Glutathione degradation by the alternative pathway (DUG pathway) in Saccharomyces cerevisiae is initiated by (Dug2p-Dug3p)2 complex, a novel glutamine amidotransferase (GATase) enzyme acting on glutathione. J Biol Chem 287: 8920–8931, 2012.
62.
Kaur H, Kumar C, Junot C, Toledano MB, and Bachhawat AK. Dug1p Is a Cys-Gly peptidase of the gamma-glutamyl cycle of Saccharomyces cerevisiae and represents a novel family of Cys-Gly peptidases. J Biol Chem 284: 14493–14502, 2009.
63.
Kawano S, Yamano K, Naoe M, Momose T, Terao K, Nishikawa S, Watanabe N, and Endo T. Structural basis of yeast Tim40/Mia40 as an oxidative translocator in the mitochondrial intermembrane space. Proc Natl Acad Sci U S A 106: 14403–14407, 2009.
64.
Keppler D, Leier I, Jedlitschky G, and Konig J. ATP-dependent transport of glutathione S-conjugates by the multidrug resistance protein MRP1 and its apical isoform MRP2. Chem Biol Interact 111–112: 153–161, 1998.
65.
Kim KD, Chung WH, Kim HJ, Lee KC, and Roe JH. Monothiol glutaredoxin Grx5 interacts with Fe-S scaffold proteins Isa1 and Isa2 and supports Fe-S assembly and DNA integrity in mitochondria of fission yeast. Biochem Biophys Res Commun 392: 467–472, 2010.
66.
Kim SJ, Woo JR, Hwang YS, Jeong DG, Shin DH, Kim K, and Ryu SE. The tetrameric structure of Haemophilus influenza hybrid Prx5 reveals interactions between electron donor and acceptor proteins. J Biol Chem 278: 10790–10798, 2003.
67.
Kistler M, Maier K, and Eckardt-Schupp F. Genetic and biochemical analysis of glutathione-deficient mutants of Saccharomyces cerevisiae. Mutagenesis 5: 39–44, 1990.
68.
Kojer K, Bien M, Gangel H, Morgan B, Dick TP, and Riemer J. Glutathione redox potential in the mitochondrial intermembrane space is linked to the cytosol and impacts the Mia40 redox state. EMBO J 31: 3169–3182, 2012.
69.
Kojer K, Peleh V, Calabrese G, Herrmann JM, and Riemer J. Kinetic control by limiting glutaredoxin amounts enables thiol oxidation in the reducing mitochondrial intermembrane space. Mol Biol Cell 26: 195–204, 2015.
70.
Kumar A, Tikoo S, Maity S, Sengupta S, Sengupta S, Kaur A, and Bachhawat AK. Mammalian proapoptotic factor ChaC1 and its homologues function as gamma-glutamyl cyclotransferases acting specifically on glutathione. EMBO Rep 13: 1095–1101, 2012.
71.
Kumar C, Igbaria A, D'Autreaux B, Planson AG, Junot C, Godat E, Bachhawat AK, Delaunay-Moisan A, and Toledano MB. Glutathione revisited: a vital function in iron metabolism and ancillary role in thiol-redox control. EMBO J 30: 2044–2056, 2011.
72.
Lee AC, Xu X, Blachly-Dyson E, Forte M, and Colombini M. The role of yeast VDAC genes on the permeability of the mitochondrial outer membrane. J Membr Biol 161: 173–181, 1998.
73.
Lee JC, Straffon MJ, Jang TY, Higgins VJ, Grant CM, and Dawes IW. The essential and ancillary role of glutathione in Saccharomyces cerevisiae analysed using a grande gsh1 disruptant strain. FEMS Yeast Res 1: 57–65, 2001.
74.
Li ZS, Lu YP, Zhen RG, Szczypka M, Thiele DJ, and Rea PA. A new pathway for vacuolar cadmium sequestration in Saccharomyces cerevisiae: YCF1-catalyzed transport of bis(glutathionato)cadmium. Proc Natl Acad Sci U S A 94: 42–47, 1997.
75.
Li ZS, Szczypka M, Lu YP, Thiele DJ, and Rea PA. The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate pump. J Biol Chem 271: 6509–6517, 1996.
76.
Lu SC. Glutathione synthesis. Biochim Biophys Acta 1830: 3143–3153, 2013.
77.
Ma XX, Jiang YL, He YX, Bao R, Chen Y, and Zhou CZ. Structures of yeast glutathione-S-transferase Gtt2 reveal a new catalytic type of GST family. EMBO Rep 10: 1320–1326, 2009.
78.
Mailloux RJ and Harper ME. Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radic Biol Med 51: 1106–1115, 2011.
79.
Mailloux RJ, Seifert EL, Bouillaud F, Aguer C, Collins S, and Harper ME. Glutathionylation acts as a control switch for uncoupling proteins UCP2 and UCP3. J Biol Chem 286: 21865–21875, 2011.
80.
Manevich Y, Feinstein SI, and Fisher AB. Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with pi GST. Proc Natl Acad Sci U S A 101: 3780–3785, 2004.
81.
Mehdi K, Thierie J, and Penninckx MJ. gamma-Glutamyl transpeptidase in the yeast Saccharomyces cerevisiae and its role in the vacuolar transport and metabolism of glutathione. Biochem J 359: 631–637, 2001.
82.
Meister A and Anderson ME. Glutathione. Annu Rev Biochem 52: 711–760, 1983.
83.
Mering C, Krause R, Snel B, Cornell M, Oliver SG, Fields S, and Bork P. Comparative assessment of large-scale data sets of protein-protein interactions. Nature 417: 399–403, 2002.
84.
Minich T, Riemer J, Schulz JB, Wielinga P, Wijnholds J, and Dringen R. The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes. J Neurochem 97: 373–384, 2006.
85.
Miyagi H, Kawai S, and Murata K. Two sources of mitochondrial NADPH in the yeast Saccharomyces cerevisiae. J Biol Chem 284: 7553–7560, 2009.
86.
Molina MM, Belli G, de la Torre MA, Rodriguez-Manzaneque MT, and Herrero E. Nuclear monothiol glutaredoxins of Saccharomyces cerevisiae can function as mitochondrial glutaredoxins. J Biol Chem 279: 51923–51930, 2004.
87.
Montero D, Tachibana C, Rahr Winther J, and Appenzeller-Herzog C. Intracellular glutathione pools are heterogeneously concentrated. Redox Biol 1: 508–513, 2013.
88.
Morgan B. Reassessing cellular glutathione homoeostasis: novel insights revealed by genetically encoded redox probes. Biochem Soc Trans 42: 979–984, 2014.
89.
Morgan B, Ezerina D, Amoako TN, Riemer J, Seedorf M, and Dick TP. Multiple glutathione disulfide removal pathways mediate cytosolic redox homeostasis. Nat Chem Biol 9: 119–125, 2013.
90.
Morgan B, Sobotta MC, and Dick TP. Measuring E(GSH) and H2O2 with roGFP2-based redox probes. Free Radic Biol Med 51: 1943–1951, 2011.
91.
Morgan B, Van Laer K, Owusu TN, Ezerina D, Pastor-Flores D, Amponsah PS, Tursch A, and Dick TP. Real-time monitoring of basal HO levels with peroxiredoxin-based probes. Nat Chem Biol 12: 437–443, 2016.
92.
Ng CH, Tan SX, Perrone GG, Thorpe GW, Higgins VJ, and Dawes IW. Adaptation to hydrogen peroxide in Saccharomyces cerevisiae: the role of NADPH-generating systems and the SKN7 transcription factor. Free Radic Biol Med 44: 1131–1145, 2008.
93.
Nickel AG, von Hardenberg A, Hohl M, Loffler JR, Kohlhaas M, Becker J, Reil JC, Kazakov A, Bonnekoh J, Stadelmaier M, Puhl SL, Wagner M, Bogeski I, Cortassa S, Kappl R, Pasieka B, Lafontaine M, Lancaster CR, Blacker TS, Hall AR, Duchen MR, Kastner L, Lipp P, Zeller T, Muller C, Knopp A, Laufs U, Bohm M, Hoth M, and Maack C. Reversal of mitochondrial transhydrogenase causes oxidative stress in heart failure. Cell Metab 22: 472–484, 2015.
94.
Nilsson R, Jain M, Madhusudhan N, Sheppard NG, Strittmatter L, Kampf C, Huang J, Asplund A, and Mootha VK. Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer. Nat Commun 5: 3128, 2014.
95.
Ohtake Y and Yabuuchi S. Molecular cloning of the gamma-glutamylcysteine synthetase gene of Saccharomyces cerevisiae. Yeast 7: 953–961, 1991.
96.
Ostergaard H, Henriksen A, Hansen FG, and Winther JR. Shedding light on disulfide bond formation: engineering a redox switch in green fluorescent protein. EMBO J 20: 5853–5862, 2001.
97.
Ostergaard H, Tachibana C, and Winther JR. Monitoring disulfide bond formation in the eukaryotic cytosol. J Cell Biol 166: 337–345, 2004.
98.
Outten CE and Culotta VC. A novel NADH kinase is the mitochondrial source of NADPH in Saccharomyces cerevisiae. EMBO J 22: 2015–2024, 2003.
99.
Outten CE and Culotta VC. Alternative start sites in the Saccharomyces cerevisiae GLR1 gene are responsible for mitochondrial and cytosolic isoforms of glutathione reductase. J Biol Chem 279: 7785–7791, 2004.
100.
Outten CE, Falk RL, and Culotta VC. Cellular factors required for protection from hyperoxia toxicity in Saccharomyces cerevisiae. Biochem J 388: 93–101, 2005.
101.
Park SG, Cha MK, Jeong W, and Kim IH. Distinct physiological functions of thiol peroxidase isoenzymes in Saccharomyces cerevisiae. J Biol Chem 275: 5723–5732, 2000.
102.
Pedrajas JR, McDonagh B, Hernandez-Torres F, Miranda-Vizuete A, Gonzalez-Ojeda R, Martinez-Galisteo E, Padilla CA, and Barcena JA. Glutathione is the resolving thiol for thioredoxin peroxidase activity of 1-Cys peroxiredoxin without being consumed during the catalytic cycle. Antioxid Redox Signal 24: 115–128, 2016.
103.
Pedrajas JR, Miranda-Vizuete A, Javanmardy N, Gustafsson JA, and Spyrou G. Mitochondria of Saccharomyces cerevisiae contain one-conserved cysteine type peroxiredoxin with thioredoxin peroxidase activity. J Biol Chem 275: 16296–16301, 2000.
104.
Pedrajas JR, Padilla CA, McDonagh B, and Barcena JA. Glutaredoxin participates in the reduction of peroxides by the mitochondrial 1-CYS peroxiredoxin in Saccharomyces cerevisiae. Antioxid Redox Signal 13: 249–258, 2010.
105.
Pedrajas JR, Porras P, Martinez-Galisteo E, Padilla CA, Miranda-Vizuete A, and Barcena JA. Two isoforms of Saccharomyces cerevisiae glutaredoxin 2 are expressed in vivo and localize to different subcellular compartments. Biochem J 364: 617–623, 2002.
106.
Porras P, McDonagh B, Pedrajas JR, Barcena JA, and Padilla CA. Structure and function of yeast glutaredoxin 2 depend on postranslational processing and are related to subcellular distribution. Biochim Biophys Acta 1804: 839–845, 2010.
107.
Porras P, Padilla CA, Krayl M, Voos W, and Barcena JA. One single in-frame AUG codon is responsible for a diversity of subcellular localizations of glutaredoxin 2 in Saccharomyces cerevisiae. J Biol Chem 281: 16551–16562, 2006.
108.
Prokisch H, Scharfe C, Camp DG, 2nd, Xiao W, David L, Andreoli C, Monroe ME, Moore RJ, Gritsenko MA, Kozany C, Hixson KK, Mottaz HM, Zischka H, Ueffing M, Herman ZS, Davis RW, Meitinger T, Oefner PJ, Smith RD, and Steinmetz LM. Integrative analysis of the mitochondrial proteome in yeast. PLoS Biol 2: e160, 2004.
109.
Rebbeor JF, Connolly GC, Dumont ME, and Ballatori N. ATP-dependent transport of reduced glutathione on YCF1, the yeast orthologue of mammalian multidrug resistance associated proteins. J Biol Chem 273: 33449–33454, 1998.
110.
Reinders J, Zahedi RP, Pfanner N, Meisinger C, and Sickmann A. Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics. J Proteome Res 5: 1543–1554, 2006.
111.
Renvoise M, Bonhomme L, Davanture M, Valot B, Zivy M, and Lemaire C. Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae. J Proteomics 106: 140–150, 2014.
112.
Richman PG and Meister A. Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. J Biol Chem 250: 1422–1426, 1975.
113.
Riemer J, Bulleid N, and Herrmann JM. Disulfide formation in the ER and mitochondria: two solutions to a common process. Science 324: 1284–1287, 2009.
114.
Rodriguez-Manzaneque MT, Tamarit J, Belli G, Ros J, and Herrero E. Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulfur enzymes. Mol Biol Cell 13: 1109–1121, 2002.
115.
Samanta MP and Liang S. Predicting protein functions from redundancies in large-scale protein interaction networks. Proc Natl Acad Sci U S A 100: 12579–12583, 2003.
116.
Schaedler TA, Thornton JD, Kruse I, Schwarzlander M, Meyer AJ, van Veen HW, and Balk J. A conserved mitochondrial ATP-binding cassette transporter exports glutathione polysulfide for cytosolic metal cofactor assembly. J Biol Chem 289: 23264–23274, 2014.
117.
Schwarzlander M, Dick TP, Meye AJ, and Morgan B. Dissecting redox biology using fluorescent protein sensors. Antioxid Redox Signal 24: 680–712, 2016.
118.
Sickmann A, Reinders J, Wagner Y, Joppich C, Zahedi R, Meyer HE, Schonfisch B, Perschil I, Chacinska A, Guiard B, Rehling P, Pfanner N, and Meisinger C. The proteome of Saccharomyces cerevisiae mitochondria. Proc Natl Acad Sci U S A 100: 13207–13212, 2003.
119.
Springael JY and Penninckx MJ. Nitrogen-source regulation of yeast gamma-glutamyl transpeptidase synthesis involves the regulatory network including the GATA zinc-finger factors Gln3, Nil1/Gat1 and Gzf3. Biochem J 371: 589–595, 2003.
120.
Srinivasan V, Pierik AJ, and Lill R. Crystal structures of nucleotide-free and glutathione-bound mitochondrial ABC transporter Atm1. Science 343: 1137–1140, 2014.
121.
Starke DW, Chock PB, and Mieyal JJ. Glutathione-thiyl radical scavenging and transferase properties of human glutaredoxin (thioltransferase). Potential role in redox signal transduction. J Biol Chem 278: 14607–14613, 2003.
122.
Stephen DW, Rivers SL, and Jamieson DJ. The role of the YAP1 and YAP2 genes in the regulation of the adaptive oxidative stress responses of Saccharomyces cerevisiae. Mol Microbiol 16: 415–423, 1995.
123.
Sugiyama K, Izawa S, and Inoue Y. The Yap1p-dependent induction of glutathione synthesis in heat shock response of Saccharomyces cerevisiae. J Biol Chem 275: 15535–15540, 2000.
124.
Szczechowicz A, Hryniewiecka L, and Kmita H. The influence of depletion of voltage dependent anion selective channel on protein import into the yeast Saccharomyces cerevisiae mitochondria. Acta Biochim Pol 48: 719–728, 2001.
125.
Tan SX, Greetham D, Raeth S, Grant CM, Dawes IW, and Perrone GG. The thioredoxin-thioredoxin reductase system can function in vivo as an alternative system to reduce oxidized glutathione in Saccharomyces cerevisiae. J Biol Chem 285: 6118–6126, 2010.
126.
Tanaka T, Izawa S, and Inoue Y. GPX2, encoding a phospholipid hydroperoxide glutathione peroxidase homologue, codes for an atypical 2-Cys peroxiredoxin in Saccharomyces cerevisiae. J Biol Chem 280: 42078–42087, 2005.
127.
Tatsuta T, Scharwey M, and Langer T. Mitochondrial lipid trafficking. Trends Cell Biol 24: 44–52, 2014.
128.
Trotter EW and Grant CM. Overlapping roles of the cytoplasmic and mitochondrial redox regulatory systems in the yeast Saccharomyces cerevisiae. Eukaryot Cell 4: 392–400, 2005.
129.
Ubiyvovk VM, Blazhenko OV, Gigot D, Penninckx M, and Sibirny AA. Role of gamma-glutamyltranspeptidase in detoxification of xenobiotics in the yeasts Hansenula polymorpha and Saccharomyces cerevisiae. Cell Biol Int 30: 665–671, 2006.
130.
Ubiyvovk VM, Maszewski J, Bartosz G, and Sibirny AA. Vacuolar accumulation and extracellular extrusion of electrophilic compounds by wild-type and glutathione-deficient mutants of the methylotrophic yeast Hansenula polymorpha. Cell Biol Int 27: 785–789, 2003.
131.
van der Laan M, Horvath SE, and Pfanner N. Mitochondrial contact site and cristae organizing system. Curr Opin Cell Biol 41: 33–42, 2016.
132.
Van Laer K, Hamilton CJ, and Messens J. Low-molecular-weight thiols in thiol-disulfide exchange. Antioxid Redox Signal 18: 1642–1653, 2013.
133.
Vogtle FN, Burkhart JM, Rao S, Gerbeth C, Hinrichs J, Martinou JC, Chacinska A, Sickmann A, Zahedi RP, and Meisinger C. Intermembrane space proteome of yeast mitochondria. Mol Cell Proteomics 11: 1840–1852, 2012.
134.
Vogtle FN, Wortelkamp S, Zahedi RP, Becker D, Leidhold C, Gevaert K, Kellermann J, Voos W, Sickmann A, Pfanner N, and Meisinger C. Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability. Cell 139: 428–439, 2009.
135.
Wheeler GL, Quinn KA, Perrone G, Dawes IW, and Grant CM. Glutathione regulates the expression of gamma-glutamylcysteine synthetase via the Met4 transcription factor. Mol Microbiol 46: 545–556, 2002.
136.
Wilkens V, Kohl W, and Busch K. Restricted diffusion of OXPHOS complexes in dynamic mitochondria delays their exchange between cristae and engenders a transitory mosaic distribution. J Cell Sci 126: 103–116, 2013.
137.
Wingert RA, Galloway JL, Barut B, Foott H, Fraenkel P, Axe JL, Weber GJ, Dooley K, Davidson AJ, Schmid B, Paw BH, Shaw GC, Kingsley P, Palis J, Schubert H, Chen O, Kaplan J, Zon LI, and Tubingen Screen C. Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis. Nature 436: 1035–1039, 2005.
138.
Yang M, Cobine PA, Molik S, Naranuntarat A, Lill R, Winge DR, and Culotta VC. The effects of mitochondrial iron homeostasis on cofactor specificity of superoxide dismutase 2. EMBO J 25: 1775–1783, 2006.
139.
Zechmann B, Liou LC, Koffler BE, Horvat L, Tomasic A, Fulgosi H, and Zhang Z. Subcellular distribution of glutathione and its dynamic changes under oxidative stress in the yeast Saccharomyces cerevisiae. FEMS Yeast Res 11: 631–642, 2011.
140.
Zhu Y, Sun J, Zhu Y, Wang L, and Qi B. Endogenic oxidative stress response contributes to glutathione over-accumulation in mutant Saccharomyces cerevisiae Y518. Appl Microbiol Biotechnol 99: 7069–7078, 2015.
Information & Authors
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Published In
Antioxidants & Redox Signaling
Volume 27 • Issue Number 15 • November 20, 2017
Pages: 1162 - 1177
PubMed: 28558477
Copyright
Copyright 2017, Mary Ann Liebert, Inc.
History
Published in print: November 20, 2017
Published online: 20 November 2017
Published ahead of print: 30 June 2017
Published ahead of production: 30 May 2017
Accepted: 22 May 2017
Received: 12 May 2017
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