title: Regulation of mitochondrial protein import by cytosolic kinases.
abstract: Mitochondria import a large number of nuclear-encoded proteins via membrane-bound transport machineries; however, little is known about regulation of the preprotein translocases. We report that the main protein entry gate of mitochondria, the translocase of the outer membrane (TOM complex), is phosphorylated by cytosolic kinases-in particular, casein kinase 2 (CK2) and protein kinase A (PKA). CK2 promotes biogenesis of the TOM complex by phosphorylation of two key components, the receptor Tom22 and the import protein Mim1, which in turn are required for import of further Tom proteins. Inactivation of CK2 decreases the levels of the TOM complex and thus mitochondrial protein import. PKA phosphorylates Tom70 under nonrespiring conditions, thereby inhibiting its receptor activity and the import of mitochondrial metabolite carriers. We conclude that cytosolic kinases exert stimulatory and inhibitory effects on biogenesis and function of the TOM complex and thus regulate protein import into mitochondria.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, Freiburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schmidt
authors.forename: Angelika B
authors.initials: AB
authors.lastname: Harbauer
authors.forename: Sanjana
authors.initials: S
authors.lastname: Rao
authors.forename: Beate
authors.initials: B
authors.lastname: Eyrich
authors.forename: René P
authors.initials: RP
authors.lastname: Zahedi
authors.forename: Diana
authors.initials: D
authors.lastname: Stojanovski
authors.forename: Birgit
authors.initials: B
authors.lastname: Schönfisch
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Albert
authors.initials: A
authors.lastname: Sickmann
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D047390:Casein Kinase II / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D047390:Casein Kinase II; D017868:Cyclic AMP-Dependent Protein Kinases