title: Detailed analysis of the human mitochondrial contact site complex indicate a hierarchy of subunits.
abstract: Mitochondrial inner membrane folds into cristae, which significantly increase its surface and are important for mitochondrial function. The stability of cristae depends on the mitochondrial contact site (MICOS) complex. In human mitochondria, the inner membrane MICOS complex interacts with the outer membrane sorting and assembly machinery (SAM) complex, to form the mitochondrial intermembrane space bridging complex (MIB). We have created knockdown cell lines of most of the MICOS and MIB components and have used them to study the importance of the individual subunits for the cristae formation and complex stability. We show that the most important subunits of the MIB complex in human mitochondria are Mic60/Mitofilin, Mic19/CHCHD3 and an outer membrane component Sam50. We provide additional proof that ApoO indeed is a subunit of the MICOS and MIB complexes and propose the name Mic23 for this protein. According to our results, Mic25/CHCHD6, Mic27/ApoOL and Mic23/ApoO appear to be periphery subunits of the MICOS complex, because their depletion does not affect cristae morphology or stability of other components.
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Ott
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Dorsch
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Fraunholz
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Straub
authors.affiliation: Biocenter, Chair of Microbiology, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Kozjak-Pavlovic
mesh_terms: D001053:Apolipoproteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D021122:Protein Subunits / Q000378:metabolism
chemical_list: C585262:APOOL protein, human; C000589295:APOO protein, human; D001053:Apolipoproteins; C521110:CHCHD3 protein, human; C522814:CHCHD6 protein, human; D008565:Membrane Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D021122:Protein Subunits; C522815:SAMM50 protein, human