MIA40

Summary

Gene Symbol: MIA40
Description: Mia40p
Alias: FMP15, TIM40, Mia40p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Kawano S, Yamano K, Naoé M, Momose T, Terao K, Nishikawa S, et al. Structural basis of yeast Tim40/Mia40 as an oxidative translocator in the mitochondrial intermembrane space. Proc Natl Acad Sci U S A. 2009;106:14403-7 pubmed publisher
    ..outer membrane and subsequent folding require recognition and disulfide bond transfer by an oxidative translocator Tim40/Mia40 in the inner membrane facing the IMS...
  2. Gebert N, Chacinska A, Wagner K, Guiard B, Koehler C, Rehling P, et al. Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase. EMBO Rep. 2008;9:548-54 pubmed publisher
  3. Müller J, Milenkovic D, Guiard B, Pfanner N, Chacinska A. Precursor oxidation by Mia40 and Erv1 promotes vectorial transport of proteins into the mitochondrial intermembrane space. Mol Biol Cell. 2008;19:226-36 pubmed
    ..Import of the precursors requires the essential intermembrane space proteins Mia40 and Erv1 that were proposed to form a relay for disulfide formation in the precursor proteins...
  4. Grumbt B, Stroobant V, Terziyska N, Israel L, Hell K. Functional characterization of Mia40p, the central component of the disulfide relay system of the mitochondrial intermembrane space. J Biol Chem. 2007;282:37461-70 pubmed
    b>Mia40p and Erv1p are components of a translocation pathway for the import of cysteine-rich proteins into the intermembrane space of mitochondria...
  5. Chacinska A, Pfannschmidt S, Wiedemann N, Kozjak V, Sanjuán Szklarz L, Schulze Specking A, et al. Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins. EMBO J. 2004;23:3735-46 pubmed
    ..We have identified the essential IMS protein Mia40 (encoded by the Saccharomyces cerevisiae open reading frame YKL195w)...
  6. Bien M, Longen S, Wagener N, Chwalla I, Herrmann J, Riemer J. Mitochondrial disulfide bond formation is driven by intersubunit electron transfer in Erv1 and proofread by glutathione. Mol Cell. 2010;37:516-28 pubmed publisher
    ..Major players in this pathway are the oxidoreductase Mia40 that oxidizes substrates and the sulfhydryl oxidase Erv1 that reoxidizes Mia40...
  7. Stojanovski D, Milenkovic D, Müller J, Gabriel K, Schulze Specking A, Baker M, et al. Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase. J Cell Biol. 2008;183:195-202 pubmed publisher
    ..a transient and intermediate step in the oxidation of intermembrane space precursors, where the oxidase Erv1 promotes disulfide transfer to the precursor while both oxidase and precursor are associated with the disulfide carrier Mia40.
  8. Böttinger L, Gornicka A, Czerwik T, Bragoszewski P, Loniewska Lwowska A, Schulze Specking A, et al. In vivo evidence for cooperation of Mia40 and Erv1 in the oxidation of mitochondrial proteins. Mol Biol Cell. 2012;23:3957-69 pubmed publisher
    ..pathway is based on a relay of reactions involving disulfide transfer from the sulfhydryl oxidase Erv1 to Mia40 and from Mia40 to substrate proteins. However, the substrates of the MIA typically contain two disulfide bonds...
  9. Weckbecker D, Longen S, Riemer J, Herrmann J. Atp23 biogenesis reveals a chaperone-like folding activity of Mia40 in the IMS of mitochondria. EMBO J. 2012;31:4348-58 pubmed publisher
    b>Mia40 is a recently identified oxidoreductase in the intermembrane space (IMS) of mitochondria that mediates protein import in an oxidation-dependent reaction...

More Information

Publications45

  1. Sideris D, Tokatlidis K. Oxidative folding of small Tims is mediated by site-specific docking onto Mia40 in the mitochondrial intermembrane space. Mol Microbiol. 2007;65:1360-73 pubmed
    ..The essential proteins Mia40 and Erv1 are key components for this mechanism functioning as a disulphide protein cascade that is functionally ..
  2. Rissler M, Wiedemann N, Pfannschmidt S, Gabriel K, Guiard B, Pfanner N, et al. The essential mitochondrial protein Erv1 cooperates with Mia40 in biogenesis of intermembrane space proteins. J Mol Biol. 2005;353:485-92 pubmed
    ..The biogenesis of small IMS proteins requires an essential mitochondrial IMS import and assembly protein, termed Mia40. Here, we show that Erv1, a further essential IMS protein that has been reported to function as a sulfhydryl ..
  3. Terziyska N, Lutz T, Kozany C, Mokranjac D, Mesecke N, Neupert W, et al. Mia40, a novel factor for protein import into the intermembrane space of mitochondria is able to bind metal ions. FEBS Lett. 2005;579:179-84 pubmed
    ..We have identified an essential component, Mia40/Tim40/Ykl195w, with a highly conserved domain in the IMS that is able to bind zinc and copper ions...
  4. Klöppel C, Suzuki Y, Kojer K, Petrungaro C, Longen S, Fiedler S, et al. Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol. Mol Biol Cell. 2011;22:3749-57 pubmed publisher
    ..pathway of Ccs1 and characterize its interaction with the oxidoreductase of the mitochondrial disulfide relay Mia40. We identify cysteines at positions 27 and 64 in domain I of Ccs1 as critical for mitochondrial import and ..
  5. Lionaki E, Aivaliotis M, Pozidis C, Tokatlidis K. The N-terminal shuttle domain of Erv1 determines the affinity for Mia40 and mediates electron transfer to the catalytic Erv1 core in yeast mitochondria. Antioxid Redox Signal. 2010;13:1327-39 pubmed publisher
    Erv1 and Mia40 constitute the two important components of the disulfide relay system that mediates oxidative protein folding in the mitochondrial intermembrane space...
  6. Sideris D, Petrakis N, Katrakili N, Mikropoulou D, Gallo A, Ciofi Baffoni S, et al. A novel intermembrane space-targeting signal docks cysteines onto Mia40 during mitochondrial oxidative folding. J Cell Biol. 2009;187:1007-22 pubmed publisher
    b>Mia40 imports Cys-containing proteins into the mitochondrial intermembrane space (IMS) by ensuring their Cys-dependent oxidative folding...
  7. Tienson H, Dabir D, Neal S, Loo R, Hasson S, Boontheung P, et al. Reconstitution of the mia40-erv1 oxidative folding pathway for the small tim proteins. Mol Biol Cell. 2009;20:3481-90 pubmed publisher
    b>Mia40 and Erv1 execute a disulfide relay to import the small Tim proteins into the mitochondrial intermembrane space...
  8. Terziyska N, Grumbt B, Kozany C, Hell K. Structural and functional roles of the conserved cysteine residues of the redox-regulated import receptor Mia40 in the intermembrane space of mitochondria. J Biol Chem. 2009;284:1353-63 pubmed publisher
    ..This import pathway employs a disulfide relay system whose key components are the redox-regulated import receptor Mia40 and the thiol oxidase Erv1...
  9. Reddehase S, Grumbt B, Neupert W, Hell K. The disulfide relay system of mitochondria is required for the biogenesis of mitochondrial Ccs1 and Sod1. J Mol Biol. 2009;385:331-8 pubmed publisher
    ..The IMS of mitochondria harbors a disulfide relay system consisting of the import receptor Mia40 and the thiol oxidase Erv1, which drives the import of substrates with conserved cysteine residues arranged in ..
  10. Bourens M, Dabir D, Tienson H, Sorokina I, Koehler C, Barrientos A. Role of twin Cys-Xaa9-Cys motif cysteines in mitochondrial import of the cytochrome C oxidase biogenesis factor Cmc1. J Biol Chem. 2012;287:31258-69 pubmed publisher
    The Mia40 import pathway facilitates the import and oxidative folding of cysteine-rich protein substrates into the mitochondrial intermembrane space...
  11. Mesecke N, Terziyska N, Kozany C, Baumann F, Neupert W, Hell K, et al. A disulfide relay system in the intermembrane space of mitochondria that mediates protein import. Cell. 2005;121:1059-69 pubmed
    ..After passage through the TOM channel, these proteins are covalently trapped by Mia40 via disulfide bridges. Mia40 contains cysteine residues, which are oxidized by the sulfhydryl oxidase Erv1...
  12. Wrobel L, Trojanowska A, Sztolsztener M, Chacinska A. Mitochondrial protein import: Mia40 facilitates Tim22 translocation into the inner membrane of mitochondria. Mol Biol Cell. 2013;24:543-54 pubmed publisher
    ..The oxidoreductase Mia40 is a central component of the pathway responsible for the transfer of disulfide bonds to intermembrane space ..
  13. Dabir D, Leverich E, Kim S, Tsai F, Hirasawa M, Knaff D, et al. A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1. EMBO J. 2007;26:4801-11 pubmed
    ..By coupling these pathways, cytochrome c and Ccp1 function efficiently as Erv1-dependent electron acceptors. Thus, we propose that Erv1 utilizes diverse pathways for electron shuttling in the IMS. ..
  14. Spiller M, Ang S, Ceh Pavia E, Fisher K, Wang Q, Rigby S, et al. Identification and characterization of mitochondrial Mia40 as an iron-sulfur protein. Biochem J. 2013;455:27-35 pubmed publisher
    b>Mia40 is a highly conserved mitochondrial protein that plays an essential role in the import and oxidative folding of many proteins of the mitochondrial intermembrane space...
  15. Naoé M, Ohwa Y, Ishikawa D, Ohshima C, Nishikawa S, Yamamoto H, et al. Identification of Tim40 that mediates protein sorting to the mitochondrial intermembrane space. J Biol Chem. 2004;279:47815-21 pubmed
    ..Here we identified a new inner membrane protein, Tim40, that mediates sorting of small Tim proteins to the intermembrane space...
  16. Kojer K, Bien M, Gangel H, Morgan B, Dick T, Riemer J. Glutathione redox potential in the mitochondrial intermembrane space is linked to the cytosol and impacts the Mia40 redox state. EMBO J. 2012;31:3169-82 pubmed publisher
    ..Moreover, we show that the local E(GSH) contributes to the partially reduced redox state of the IMS oxidoreductase Mia40 in vivo...
  17. Chacinska A, Guiard B, Müller J, Schulze Specking A, Gabriel K, Kutik S, et al. Mitochondrial biogenesis, switching the sorting pathway of the intermembrane space receptor Mia40. J Biol Chem. 2008;283:29723-9 pubmed publisher
    ..We report that the intermembrane space receptor Mia40 can switch between both pathways...
  18. Milenkovic D, Gabriel K, Guiard B, Schulze Specking A, Pfanner N, Chacinska A. Biogenesis of the essential Tim9-Tim10 chaperone complex of mitochondria: site-specific recognition of cysteine residues by the intermembrane space receptor Mia40. J Biol Chem. 2007;282:22472-80 pubmed
    ..Biogenesis of IMS proteins involves a disulfide relay between precursor proteins, the cysteine-rich IMS protein Mia40 and the sulfhydryl oxidase Erv1. How precursor proteins are specifically directed to the IMS has remained unknown...
  19. Terziyska N, Grumbt B, Bien M, Neupert W, Herrmann J, Hell K. The sulfhydryl oxidase Erv1 is a substrate of the Mia40-dependent protein translocation pathway. FEBS Lett. 2007;581:1098-102 pubmed
    The thiol oxidase Erv1 and the redox-regulated receptor Mia40/Tim40 are components of a disulfide relay system which mediates import of proteins into the intermembrane space (IMS) of mitochondria...
  20. Peleh V, Cordat E, Herrmann J. Mia40 is a trans-site receptor that drives protein import into the mitochondrial intermembrane space by hydrophobic substrate binding. elife. 2016;5: pubmed publisher
    ..The conserved IMS protein Mia40 is essential for the oxidation and import of these proteins...
  21. Chojnacka M, Gornicka A, Oeljeklaus S, Warscheid B, Chacinska A. Cox17 Protein Is an Auxiliary Factor Involved in the Control of the Mitochondrial Contact Site and Cristae Organizing System. J Biol Chem. 2015;290:15304-12 pubmed publisher
    ..However, the Cox17-MICOS interaction is regulated by copper ions. We propose that Cox17 is a newly identified factor involved in maintaining the architecture of the MICOS complex. ..
  22. Koch J, Schmid F. Mia40 combines thiol oxidase and disulfide isomerase activity to efficiently catalyze oxidative folding in mitochondria. J Mol Biol. 2014;426:4087-98 pubmed publisher
    b>Mia40 (a mitochondrial import and assembly protein) catalyzes disulfide bond formation in proteins in the mitochondrial intermembrane space...
  23. Koch J, Schmid F. Mia40 is optimized for function in mitochondrial oxidative protein folding and import. ACS Chem Biol. 2014;9:2049-57 pubmed publisher
    b>Mia40 catalyzes oxidative protein folding in mitochondria. It contains a unique catalytic CPC dithiol flanked by a hydrophobic groove, and unlike other oxidoreductases, it forms long-lived mixed disulfides with substrates...
  24. Ang S, Zhang M, Lodi T, Lu H. Mitochondrial thiol oxidase Erv1: both shuttle cysteine residues are required for its function with distinct roles. Biochem J. 2014;460:199-210 pubmed publisher
    ..In the MIA pathway, Mia40, a thiol oxidoreductase with a CPC motif at its active site, oxidizes newly imported substrate proteins...
  25. Ramesh A, Peleh V, Martinez Caballero S, Wollweber F, Sommer F, van der Laan M, et al. A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import. J Cell Biol. 2016;214:417-31 pubmed publisher
    ..Whereas the import of Tim17 depends on the binding to the IMS protein Mia40, the oxidoreductase activity of Mia40 is surprisingly dispensable for Tim17 oxidation...
  26. Fraga H, Bech Serra J, Canals F, Ortega G, Millet O, Ventura S. The mitochondrial intermembrane space oxireductase Mia40 funnels the oxidative folding pathway of the cytochrome c oxidase assembly protein Cox19. J Biol Chem. 2014;289:9852-64 pubmed publisher
    b>Mia40-catalyzed disulfide formation drives the import of many proteins into the mitochondria. Here we characterize the oxidative folding of Cox19, a twin CX9C Mia40 substrate...
  27. Koch J, Schmid F. Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria. Nat Commun. 2014;5:3041 pubmed publisher
    b>Mia40 catalyses the oxidative folding of disulphide-containing proteins in the mitochondria. The folding pathway is directed by the formation of the first mixed disulphide between Mia40 and its substrate...
  28. Longen S, Woellhaf M, Petrungaro C, Riemer J, Herrmann J. The disulfide relay of the intermembrane space oxidizes the ribosomal subunit mrp10 on its transit into the mitochondrial matrix. Dev Cell. 2014;28:30-42 pubmed publisher
    ..In contrast, the import of many intermembrane space proteins depends on cysteine residues and the oxidoreductase Mia40. Here, we show that both import machineries can cooperate in the biogenesis of matrix proteins...
  29. Chacinska A, Lind M, Frazier A, Dudek J, Meisinger C, Geissler A, et al. Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell. 2005;120:817-29 pubmed
    ..Thus, the presequence translocase is not a static complex but switches between TOM tethering and PAM binding in a reaction cycle involving Tim21 and Tim17. ..
  30. Mesecke N, Bihlmaier K, Grumbt B, Longen S, Terziyska N, Hell K, et al. The zinc-binding protein Hot13 promotes oxidation of the mitochondrial import receptor Mia40. EMBO Rep. 2008;9:1107-13 pubmed publisher
    ..This system consists of two essential proteins, Mia40 and Erv1, which bind to newly imported proteins by disulphide transfer...
  31. Gornicka A, Bragoszewski P, Chrościcki P, Wenz L, Schulz C, Rehling P, et al. A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria. Mol Biol Cell. 2014;25:3999-4009 pubmed publisher
    ..Thus MIA-dependent proteins take another route across the outer mitochondrial membrane that involves Tom40 in a form that is different from the canonical TOM complex. ..
  32. Varabyova A, Topf U, Kwiatkowska P, Wrobel L, Kaus Drobek M, Chacinska A. Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1. FEBS J. 2013;280:4943-59 pubmed publisher
    ..Localization of the reduced, Ccs1-independent forms of Sod1 relied on Mia40, an essential component of the mitochondrial intermembrane space import and assembly pathway that is responsible ..
  33. Neal S, Dabir D, Tienson H, Horn D, Glaeser K, Ogozalek Loo R, et al. Mia40 Protein Serves as an Electron Sink in the Mia40-Erv1 Import Pathway. J Biol Chem. 2015;290:20804-14 pubmed publisher
    A redox-regulated import pathway consisting of Mia40 and Erv1 mediates the import of cysteine-rich proteins into the mitochondrial intermembrane space...
  34. Shirozu R, Yashiroda H, Murata S. Proteasome Impairment Induces Recovery of Mitochondrial Membrane Potential and an Alternative Pathway of Mitochondrial Fusion. Mol Cell Biol. 2016;36:347-62 pubmed publisher
    ..Decreased proteasome activity increased the mitochondrial oxidoreductase protein Mia40 and the ratio of the short isoform of mitochondrial intermembrane protein Mgm1 (s-Mgm1) to the long isoform (l-..
  35. Banci L, Bertini I, Ciofi Baffoni S, Boscaro F, Chatzi A, Mikolajczyk M, et al. Anamorsin is a [2Fe-2S] cluster-containing substrate of the Mia40-dependent mitochondrial protein trapping machinery. Chem Biol. 2011;18:794-804 pubmed publisher
    ..Here, the structural and metal-binding properties of anamorsin and its interaction with Mia40, a well-known oxidoreductase involved in protein trapping in the mitochondrial intermembrane space (IMS), were ..
  36. Ozer H, Dlouhy A, Thornton J, Hu J, Liu Y, Barycki J, et al. Cytosolic Fe-S Cluster Protein Maturation and Iron Regulation Are Independent of the Mitochondrial Erv1/Mia40 Import System. J Biol Chem. 2015;290:27829-40 pubmed publisher
    The sulfhydryl oxidase Erv1 partners with the oxidoreductase Mia40 to import cysteine-rich proteins in the mitochondrial intermembrane space...