Biogenesis of the preprotein translocase of the outer mitochondrial membrane: protein kinase A phosphorylates the precursor of Tom40 and impairs its import
Open Access
- 1 May 2012
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 23 (9), 1618-1627
- https://doi.org/10.1091/mbc.e11-11-0933
Abstract
The preprotein translocase of the outer mitochondrial membrane (TOM) functions as the main entry gate for the import of nuclear-encoded proteins into mitochondria. The major subunits of the TOM complex are the three receptors Tom20, Tom22, and Tom70 and the central channel-forming protein Tom40. Cytosolic kinases have been shown to regulate the biogenesis and activity of the Tom receptors. Casein kinase 2 stimulates the biogenesis of Tom22 and Tom20, whereas protein kinase A (PKA) impairs the receptor function of Tom70. Here we report that PKA exerts an inhibitory effect on the biogenesis of the β-barrel protein Tom40. Tom40 is synthesized as precursor on cytosolic ribosomes and subsequently imported into mitochondria. We show that PKA phosphorylates the precursor of Tom40. The phosphorylated Tom40 precursor is impaired in import into mitochondria, whereas the nonphosphorylated precursor is efficiently imported. We conclude that PKA plays a dual role in the regulation of the TOM complex. Phosphorylation by PKA not only impairs the receptor activity of Tom70, but it also inhibits the biogenesis of the channel protein Tom40.Keywords
This publication has 89 references indexed in Scilit:
- In vivo protein-interaction mapping of a mitochondrial translocator protein Tom22 at workProceedings of the National Academy of Sciences of the United States of America, 2011
- Tom7 Regulates Mdm10-mediated Assembly of the Mitochondrial Import Channel Protein Tom40Journal of Biological Chemistry, 2010
- Assembly of the Mitochondrial Protein Import ChannelMolecular Biology of the Cell, 2010
- Molecular Chaperone Hsp70/Hsp90 Prepares the Mitochondrial Outer Membrane Translocon Receptor Tom71 for Preprotein LoadingPublished by Elsevier BV ,2009
- HowSaccharomycesResponds to NutrientsAnnual Review of Genetics, 2008
- A Multidimensional Chromatography Technology for In-depth Phosphoproteome AnalysisMolecular & Cellular Proteomics, 2008
- Mim1 Functions in an Oligomeric Form to Facilitate the Integration of Tom20 into the Mitochondrial Outer MembraneJournal of Molecular Biology, 2008
- Cyclic AMP-Protein Kinase A and Snf1 Signaling Mechanisms Underlie the Superior Potency of Sucrose for Induction of Filamentation in Saccharomyces cerevisiaeEukaryotic Cell, 2008
- The morphology proteins Mdm12/Mmm1 function in the major β-barrel assembly pathway of mitochondriaThe EMBO Journal, 2007
- Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometryProceedings of the National Academy of Sciences of the United States of America, 2007