title: Mic13 Is Essential for Formation of Crista Junctions in Mammalian Cells.
abstract: Mitochondrial cristae are connected to the inner boundary membrane via crista junctions which are implicated in the regulation of oxidative phosphorylation, apoptosis, and import of lipids and proteins. The MICOS complex determines formation of crista junctions. We performed complexome profiling and identified Mic13, also termed Qil1, as a subunit of the MICOS complex. We show that MIC13 is an inner membrane protein physically interacting with MIC60, a central subunit of the MICOS complex. Using the CRISPR/Cas method we generated the first cell line deleted for MIC13. These knockout cells show a complete loss of crista junctions demonstrating that MIC13 is strictly required for the formation of crista junctions. MIC13 is required for the assembly of MIC10, MIC26, and MIC27 into the MICOS complex. However, it is not needed for the formation of the MIC60/MIC19/MIC25 subcomplex suggesting that the latter is not sufficient for crista junction formation. MIC13 is also dispensable for assembly of respiratory chain complexes and for maintaining mitochondrial network morphology. Still, lack of MIC13 resulted in a moderate reduction of mitochondrial respiration. In summary, we show that MIC13 has a fundamental role in crista junction formation and that assembly of respiratory chain supercomplexes is independent of mitochondrial cristae shape.
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Heinrich Heine University, Medical Faculty, Universitätsstr. 1, 40225, Düsseldorf, Germany.
authors.forename: Ruchika
authors.initials: R
authors.lastname: Anand
authors.affiliation: Functional Proteomics, SFB 815 Core Unit, Faculty of Medicine, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Strecker
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Heinrich Heine University, Medical Faculty, Universitätsstr. 1, 40225, Düsseldorf, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Urbach
authors.affiliation: Functional Proteomics, SFB 815 Core Unit, Faculty of Medicine, Goethe-University, Frankfurt am Main, Germany.|Cluster of Excellence "Macromolecular Complexes", Goethe University, Frankfurt am Main, Germany.|German Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.affiliation: Institute of Biochemistry and Molecular Biology I, Heinrich Heine University, Medical Faculty, Universitätsstr. 1, 40225, Düsseldorf, Germany.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Reichert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D064113:CRISPR-Cas Systems / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010085:Oxidative Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C000621991:MICOS13 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering