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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, e104105, pp. 1-24. doi:10.15252/embj.2019104105.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-9D79-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-9D7D-E
Genre: Journal Article

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EMBOJ_epub_2020_e104105.pdf (Any fulltext), 9MB
 
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 Creators:
Stephan, Till, Author
Brüser, Christian, Author
Deckers, Markus, Author
Steyer, Anna M, Author
Balzarotti, Francisco, Author
Barbot, Mariam, Author
Behr, Tiana S, Author
Heim, Gudrun, Author
Hübner, Wolfgang, Author
Ilgen, Peter, Author
Lange, Felix, Author
Pacheu-Grau, David, Author
Pape, Jasmin K, Author
Stoldt, Stefan, Author
Huser, Thomas, Author
Hell, Stefan W.1, Author              
Möbius, Wiebke, Author
Rehling, Peter, Author
Riedel, Dietmar, Author
Jakobs, Stefan, Author
Affiliations:
1Optical Nanoscopy, Max Planck Institute for Medical Research, Max Planck Society, ou_2364730              

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Free keywords: MINFLUX; cristae biogenesis; electron microscopy; 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 F1 Fo -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 F1 Fo -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: 2020-05-082019-11-252020-05-132020-06-22
 Publication Status: Published online
 Pages: 24
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

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Title: EMBO Journal
  Other : EMBO J.
Source Genre: Journal
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Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: - Sequence Number: e104105 Start / End Page: 1 - 24 Identifier: ISSN: 0261-4189
CoNE: https://pure.mpg.de/cone/journals/resource/954925497061