MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation
Open Access
- 22 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 39 (14), e104105
- https://doi.org/10.15252/embj.2019104105
Abstract
Mitochondrial function is critically dependent on the folding of the mitochondrial inner membrane into cristae; indeed, numerous human diseases are associated with aberrant crista morphologies. With the MICOS complex, OPA1 and the F1Fo‐ATP synthase, key players of cristae biogenesis have been identified, yet their interplay is poorly understood. Harnessing super‐resolution light and 3D electron microscopy, we dissect the roles of these proteins in the formation of cristae in human mitochondria. We individually disrupted the genes of all seven MICOS subunits in human cells and re‐expressed Mic10 or Mic60 in the respective knockout cell line. We demonstrate that assembly of the MICOS complex triggers remodeling of pre‐existing unstructured cristae and de novo formation of crista junctions (CJs) on existing cristae. We show that the Mic60‐subcomplex is sufficient for CJ formation, whereas the Mic10‐subcomplex controls lamellar cristae biogenesis. OPA1 stabilizes tubular CJs and, along with the F1Fo‐ATP synthase, fine‐tunes the positioning of the MICOS complex and CJs. We propose a new model of cristae formation, involving the coordinated remodeling of an unstructured crista precursor into multiple lamellar cristae.Keywords
Funding Information
- H2020 European Research Council (835102)
- Deutsche Forschungsgemeinschaft (FOR2848; P08; Z01, SFB1190; P01; P13)
This publication has 83 references indexed in Scilit:
- MINFLUX nanoscopy delivers 3D multicolor nanometer resolution in cellsNature Methods, 2020
- Mic60 exhibits a coordinated clustered distribution along and across yeast and mammalian mitochondriaProceedings of the National Academy of Sciences of the United States of America, 2019
- Structure and Mechanisms of F-Type ATP SynthasesAnnual Review of Biochemistry, 2018
- The Yin & Yang of Mitochondrial Architecture - Interplay of MICOS and F1Fo-ATP synthase in cristae formationMicrobial Cell, 2017
- Electron tomographic analysis reveals ultrastructural features of mitochondrial cristae architecture which reflect energetic state and agingScientific Reports, 2017
- Mic10 Oligomerizes to Bend Mitochondrial Inner Membranes at Cristae JunctionsCell Metabolism, 2015
- MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organizationMolecular Biology of the Cell, 2012
- Dual Role of Mitofilin in Mitochondrial Membrane Organization and Protein BiogenesisDevelopmental Cell, 2011
- OPA1 Controls Apoptotic Cristae Remodeling Independently from Mitochondrial FusionCell, 2006
- OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28Nature Genetics, 2000