Mitochondria. Cell cycle-dependent regulation of mitochondrial preprotein translocase.
Mitochondria play central roles in cellular energy conversion, metabolism, and apoptosis. Mitochondria import more than 1000 different proteins from the cytosol. It is unknown if the mitochondrial protein import machinery is connected to the cell division cycle. We found that the cyclin-dependent kinase Cdk1 stimulated assembly of the main mitochondrial entry gate, the translocase of the outer membrane (TOM), in mitosis. The molecular mechanism involved phosphorylation of the cytosolic precursor of Tom6 by cyclin Clb3-activated Cdk1, leading to enhanced import of Tom6 into mitochondria. Tom6 phosphorylation promoted assembly of the protein import channel Tom40 and import of fusion proteins, thus stimulating the respiratory activity of mitochondria in mitosis. Tom6 phosphorylation provides a direct means for regulating mitochondrial biogenesis and activity in a cell cycle-specific manner.
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany. Trinationales Graduiertenkolleg 1478, Universität Freiburg, 79104 Freiburg, Germany. Faculty of Biology, Universität Freiburg, 79104 Freiburg, Germany. BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
Angelika B
AB
Harbauer
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Magdalena
M
Opalińska
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany. Trinationales Graduiertenkolleg 1478, Universität Freiburg, 79104 Freiburg, Germany. Faculty of Biology, Universität Freiburg, 79104 Freiburg, Germany.
Carolin
C
Gerbeth
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Josip S
JS
Herman
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany. Faculty of Biology, Universität Freiburg, 79104 Freiburg, Germany. Spemann Graduate School of Biology and Medicine, Universität Freiburg, 79104 Freiburg, Germany.
Sanjana
S
Rao
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
Birgit
B
Schönfisch
Centre de Génétique Moléculaire, CNRS, 91190 Gif-sur-Yvette, France.
Bernard
B
Guiard
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany. BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
Oliver
O
Schmidt
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany. BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany. nikolaus.pfanner@biochemie.uni-freiburg.de chris.meisinger@biochemie.uni-freiburg.de.
Nikolaus
N
Pfanner
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany. BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany. nikolaus.pfanner@biochemie.uni-freiburg.de chris.meisinger@biochemie.uni-freiburg.de.
Chris
C
Meisinger
D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D019926:Cyclin B / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010766:Phosphorylation; D011498:Protein Precursors / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
C491083:CLB3 protein, S cerevisiae; D019926:Cyclin B; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D029701:Saccharomyces cerevisiae Proteins; C082532:TOM6 protein, S cerevisiae; C066555:Tom40 protein, S cerevisiae; D016203:CDC2 Protein Kinase