Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth
Heike Rampelt,
Florian Wollweber,
Mariya Licheva,
Rinse de Boer,
Inge Perschil,
Liesa Steidle,
Thomas Becker,
Maria Bohnert,
Ida van der Klei,
Claudine Kraft,
Martin van der Laan,
Nikolaus Pfanner
Affiliations
Heike Rampelt
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany; Corresponding author
Florian Wollweber
Medical Biochemistry & Molecular Biology, Center for Molecular Signaling, PZMS, Faculty of Medicine, Saarland University, 66421 Homburg, Germany
Mariya Licheva
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany
Rinse de Boer
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9700 Groningen, the Netherlands
Inge Perschil
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
Liesa Steidle
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
Thomas Becker
Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Bonn, 53115 Bonn, Germany
Maria Bohnert
Institute of Cell Dynamics and Imaging, Cells in Motion Interfaculty Centre (CiM), University of Münster, 48149 Münster, Germany
Ida van der Klei
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9700 Groningen, the Netherlands
Claudine Kraft
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
Martin van der Laan
Medical Biochemistry & Molecular Biology, Center for Molecular Signaling, PZMS, Faculty of Medicine, Saarland University, 66421 Homburg, Germany; Corresponding author
Nikolaus Pfanner
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany; Corresponding author
Summary: Invaginations of the mitochondrial inner membrane, termed cristae, are hubs for oxidative phosphorylation. The mitochondrial contact site and cristae organizing system (MICOS) and the dimeric F1Fo-ATP synthase play important roles in controlling cristae architecture. A fraction of the MICOS core subunit Mic10 is found in association with the ATP synthase, yet it is unknown whether this interaction is of relevance for mitochondrial or cellular functions. Here, we established conditions to selectively study the role of Mic10 at the ATP synthase. Mic10 variants impaired in MICOS functions stimulate ATP synthase oligomerization like wild-type Mic10 and promote efficient inner membrane energization, adaptation to non-fermentable carbon sources, and respiratory growth. Mic10's functions in respiratory growth largely depend on Mic10ATPsynthase, not on Mic10MICOS. We conclude that Mic10 plays a dual role as core subunit of MICOS and as partner of the F1Fo-ATP synthase, serving distinct functions in cristae shaping and respiratory adaptation and growth.
