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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., et al. (2020). MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation. EMBO Journal, 39(14): e104105. doi:10.15252/embj.2019104105.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-6E35-3 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-6E3B-D
Genre: Journal Article

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 Creators:
Stephan, T.1, Author              
Brüser, C.1, Author              
Deckers, M., Author
Steyer, A. M., Author
Balzarotti, F.2, Author              
Barbot, M., Author
Behr, T. S., Author
Heim, G.3, Author              
Hübner, W., Author
Ilgen, P.2, Author              
Lange, F.4, Author              
Pacheu‐Grau, D., Author
Pape, J. K.2, Author              
Stoldt, Stefan4, Author              
Huser, T., Author
Hell, S. W.2, Author              
Möbius, W., Author
Rehling, P., Author
Riedel, Dietmar3, Author              
Jakobs, S.4, Author              
Affiliations:
1Research Group of Mitochondrial Structure and Dynamics, MPI for Biophysical Chemistry, Max Planck Society, ou_578566              
2Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society, ou_578627              
3Facility for Electron Microscopy, MPI for biophysical chemistry, Max Planck Society, ou_578615              
4Research Group of Mitochondrial Structure and Dynamics, MPI for biophysical chemistry, Max Planck Society, ou_578566              

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Free keywords: cristae biogenesis; electron microscopy; MINFLUX; nanoscopy; super-resolution microscopy
 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.

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Language(s): eng - English
 Dates: 2020-06-222020-07-15
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.15252/embj.2019104105
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Title: EMBO Journal
Source Genre: Journal
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Pages: 24 Volume / Issue: 39 (14) Sequence Number: e104105 Start / End Page: - Identifier: -