Identification of MIMAS, a multifunctional mega-assembly integrating metabolic and respiratory biogenesis factors of mitochondria
Patrick Horten,
Kuo Song,
Joshua Garlich,
Robert Hardt,
Lilia Colina-Tenorio,
Susanne E. Horvath,
Uwe Schulte,
Bernd Fakler,
Martin van der Laan,
Thomas Becker,
Rosemary A. Stuart,
Nikolaus Pfanner,
Heike Rampelt
Affiliations
Patrick Horten
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
Kuo Song
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
Joshua Garlich
Department of Biological Sciences, Marquette University, Milwaukee, WI 53233, USA
Robert Hardt
Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Bonn, 53115 Bonn, Germany
Lilia Colina-Tenorio
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
Susanne E. Horvath
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
Uwe Schulte
Institute of Physiology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
Bernd Fakler
Institute of Physiology, 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
Martin van der Laan
Medical Biochemistry and Molecular Biology, Center for Molecular Signaling, PZMS, Faculty of Medicine, Saarland University, 66421 Homburg, Germany
Thomas Becker
Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Bonn, 53115 Bonn, Germany
Rosemary A. Stuart
Department of Biological Sciences, Marquette University, Milwaukee, WI 53233, USA
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
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
Summary: The mitochondrial inner membrane plays central roles in bioenergetics and metabolism and contains several established membrane protein complexes. Here, we report the identification of a mega-complex of the inner membrane, termed mitochondrial multifunctional assembly (MIMAS). Its large size of 3 MDa explains why MIMAS has escaped detection in the analysis of mitochondria so far. MIMAS combines proteins of diverse functions from respiratory chain assembly to metabolite transport, dehydrogenases, and lipid biosynthesis but not the large established supercomplexes of the respiratory chain, ATP synthase, or prohibitin scaffold. MIMAS integrity depends on the non-bilayer phospholipid phosphatidylethanolamine, in contrast to respiratory supercomplexes whose stability depends on cardiolipin. Our findings suggest that MIMAS forms a protein-lipid mega-assembly in the mitochondrial inner membrane that integrates respiratory biogenesis and metabolic processes in a multifunctional platform.
