Regulation of Mitochondrial Protein Import by Cytosolic Kinases

• Published in: Cell Vol. 144; no. 2; pp. 227 - 239
• Main Authors: Schmidt, Oliver, Harbauer, Angelika B., Rao, Sanjana, Eyrich, Beate, Zahedi, René P., Stojanovski, Diana, Schönfisch, Birgit, Guiard, Bernard, Sickmann, Albert, Pfanner, Nikolaus, Meisinger, Chris
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21-01-2011
• Subjects: Carrier Proteins - metabolism; Casein Kinase II - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Cytosol - enzymology; Cytosol - metabolism; Mitochondria - metabolism; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Proteins - metabolism; Phosphorylation; Protein Transport; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2010.12.015

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.
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► Protein translocase of mitochondrial outer membrane (TOM) is highly phosphorylated ► Cytosolic kinases regulate biogenesis and function of the TOM complex ► Casein kinase 2 (CK2) stimulates the biogenesis of TOM receptors ► Protein kinase A (PKA) inhibits the Tom70 receptor and import of metabolite carriers