title: The Oxidation Status of Mic19 Regulates MICOS Assembly.
abstract: The function of mitochondria depends on the proper organization of mitochondrial membranes. The morphology of the inner membrane is regulated by the recently identified mitochondrial contact site and crista organizing system (MICOS) complex. MICOS mutants exhibit alterations in crista formation, leading to mitochondrial dysfunction. However, the mechanisms that underlie MICOS regulation remain poorly understood. MIC19, a peripheral protein of the inner membrane and component of the MICOS complex, was previously reported to be required for the proper function of MICOS in maintaining the architecture of the inner membrane. Here, we show that human and Saccharomyces cerevisiae MIC19 proteins undergo oxidation in mitochondria and require the mitochondrial intermembrane space assembly (MIA) pathway, which couples the oxidation and import of mitochondrial intermembrane space proteins for mitochondrial localization. Detailed analyses identified yeast Mic19 in two different redox forms. The form that contains an intramolecular disulfide bond is bound to Mic60 of the MICOS complex. Mic19 oxidation is not essential for its integration into the MICOS complex but plays a role in MICOS assembly and the maintenance of the proper inner membrane morphology. These findings suggest that Mic19 is a redox-dependent regulator of MICOS function.
authors.affiliation: International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Sakowska
authors.affiliation: Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany Department of Neurology, University Medical Center, Göttingen, Germany.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Jans
authors.affiliation: International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Karthik
authors.initials: K
authors.lastname: Mohanraj
authors.affiliation: Electron Microscopy Facility, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Riedel
authors.affiliation: Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany Department of Neurology, University Medical Center, Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jakobs
authors.affiliation: International Institute of Molecular and Cell Biology, Warsaw, Poland achacinska@iimcb.gov.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
mesh_terms: D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C521110:CHCHD3 protein, human; C000607141:MIC19 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D029701:Saccharomyces cerevisiae Proteins