MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture

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Abstract

The conserved MICOS complex functions as a primary determinant of mitochondrial inner membrane structure. We address the organization and functional roles of MICOS and identify two independent MICOS subcomplexes: Mic27/Mic10/Mic12, whose assembly is dependent on respiratory complexes and the mitochondrial lipid cardiolipin, and Mic60/Mic19, which assembles independent of these factors. Our data suggest that MICOS subcomplexes independently localize to cristae junctions and are connected via Mic19, which functions to regulate subcomplex distribution, and thus, potentially also cristae junction copy number. MICOS subunits have non-redundant functions as the absence of MICOS subcomplexes results in more severe morphological and respiratory growth defects than deletion of single MICOS subunits or subcomplexes. Mitochondrial defects resulting from MICOS loss are caused by misdistribution of respiratory complexes in the inner membrane. Together, our data are consistent with a model where MICOS, mitochondrial lipids and respiratory complexes coordinately build a functional and correctly shaped mitochondrial inner membrane.

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Jonathan R Friedman

Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, United States

Competing interests
No competing interests declared.
Arnaud Mourier

Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany

Competing interests
No competing interests declared.
Justin Yamada

Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, United States

Competing interests
No competing interests declared.
J Michael McCaffery

Integrated Imaging Center, Johns Hopkins University, Baltimore, United States

Competing interests
No competing interests declared.
Jodi Nunnari

Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, Davis, United States

For correspondence
jmnunnari@ucdavis.edu

Competing interests
Jodi Nunnari, Reviewing editor, eLife On Scientific Advisory Board of Mitobridge, and declares no financial interest related to this work..

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