MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation
2020 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation
Stephan, T. ; Brüser, C. ; Deckers, M. ; Steyer, A. M.; Balzarotti, F. ; Barbot, M. & Behr, T. S. et al. (2020)
The EMBO Journal, 39(14). DOI: https://doi.org/10.15252/embj.2019104105
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Details
- Authors
- Stephan, Till ; Brüser, Christian ; Deckers, Markus ; Steyer, Anna M.; Balzarotti, Francisco ; Barbot, Mariam ; Behr, Tiana S.; Heim, Gudrun ; Hübner, Wolfgang; Ilgen, Peter ; Lange, Felix; Pacheu‐Grau, David ; Pape, Jasmin K.; Stoldt, Stefan ; Huser, Thomas; Hell, Stefan W. ; Möbius, Wiebke ; Rehling, Peter ; Riedel, Dietmar ; Jakobs, Stefan
- 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.
- Issue Date
- 2020
- Journal
- The EMBO Journal
- Project
- EXC 2067: Multiscale Bioimaging
SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente
SFB 1190 | P01: Untersuchung der Unterschiede in der Zusammensetzung, Funktion und Position von individuellen MICOS Komplexen in einzelnen Säugerzellen
SFB 1190 | P13: Protein Transport über den mitochondrialen Carrier Transportweg
FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala
FOR 2848 | P04: Analyse der räumlichen Organisation der OXPHOS Assemblierung in Säugerzellen - Working Group
- RG Hell
RG Jakobs (Structure and Dynamics of Mitochondria)
RG Möbius
RG Rehling (Mitochondrial Protein Biogenesis)
RG Riedel - ISSN
- 0261-4189
- eISSN
- 1460-2075
- Language
- English