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MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation

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Stephan,  T.
Research Group of Mitochondrial Structure and Dynamics, MPI for Biophysical Chemistry, Max Planck Society;

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Brüser,  C.
Research Group of Mitochondrial Structure and Dynamics, MPI for Biophysical Chemistry, Max Planck Society;

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Balzarotti,  F.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

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Heim,  G.
Facility for Electron Microscopy, MPI for biophysical chemistry, Max Planck Society;

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Ilgen,  P.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

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Lange,  F.
Research Group of Mitochondrial Structure and Dynamics, MPI for biophysical chemistry, Max Planck Society;

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Pape,  J. K.
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

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Stoldt,  Stefan
Research Group of Mitochondrial Structure and Dynamics, MPI for biophysical chemistry, Max Planck Society;

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Hell,  S. W.       
Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society;

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Riedel,  Dietmar
Facility for Electron Microscopy, MPI for biophysical chemistry, Max Planck Society;

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Jakobs,  S.
Research Group of Mitochondrial Structure and Dynamics, MPI for biophysical chemistry, Max Planck Society;

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Citation

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.


Cite as: https://hdl.handle.net/21.11116/0000-0007-6E35-3
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.