title: The MICOS component Mic60 displays a conserved membrane-bending activity that is necessary for normal cristae morphology.
abstract: The inner membrane (IM) of mitochondria displays an intricate, highly folded architecture and can be divided into two domains: the inner boundary membrane adjacent to the outer membrane and invaginations toward the matrix, called cristae. Both domains are connected by narrow, tubular membrane segments called cristae junctions (CJs). The formation and maintenance of CJs is of vital importance for the organization of the mitochondrial IM and for mitochondrial and cellular physiology. The multisubunit mitochondrial contact site and cristae organizing system (MICOS) was found to be a major factor in CJ formation. In this study, we show that the MICOS core component Mic60 actively bends membranes and, when inserted into prokaryotic membranes, induces the formation of cristae-like plasma membrane invaginations. The intermembrane space domain of Mic60 has a lipid-binding capacity and induces membrane curvature even in the absence of the transmembrane helix. Mic60 homologues from α-proteobacteria display the same membrane deforming activity and are able to partially overcome the deletion of Mic60 in eukaryotic cells. Our results show that membrane bending by Mic60 is an ancient mechanism, important for cristae formation, and had already evolved before α-proteobacteria developed into mitochondria.
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, 37073 Göttingen, Germany.
authors.forename: Daryna
authors.initials: D
authors.lastname: Tarasenko
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, 37073 Göttingen, Germany.
authors.forename: Mariam
authors.identifier: 0000-0003-3293-6623
authors.initials: M
authors.lastname: Barbot
authors.affiliation: Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany.|Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: Daniel C
authors.identifier: 0000-0002-6356-9742
authors.initials: DC
authors.lastname: Jans
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, 37073 Göttingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kroppen
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.|Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37073 Göttingen, Germany.
authors.forename: Boguslawa
authors.identifier: 0000-0001-9888-4059
authors.initials: B
authors.lastname: Sadowski
authors.affiliation: Electron Microscopy Facility, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Heim
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.|Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37073 Göttingen, Germany.
authors.forename: Wiebke
authors.identifier: 0000-0002-2902-7165
authors.initials: W
authors.lastname: Möbius
authors.affiliation: Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany.|Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
authors.forename: Stefan
authors.identifier: 0000-0002-8028-3121
authors.initials: S
authors.lastname: Jakobs
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, 37073 Göttingen, Germany michael.meinecke@med.uni-goettingen.de.|European Neuroscience Institute Göttingen, 37077 Göttingen, Germany.|Göttinger Zentrum für Molekulare Biowissenschaften, 37077 Göttingen, Germany.
authors.forename: Michael
authors.identifier: 0000-0003-1414-6951
authors.initials: M
authors.lastname: Meinecke
mesh_terms: D001692:Biological Transport / Q000502:physiology; D005057:Eukaryotic Cells / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins