Mitochondrial Protein And Lipid Trafficking Toshiya Endo Faculty of Life Sciences, Kyoto Sangyo University
Since mitochondria are only generated by growth and division of preexisting mitochondria or require them as templates, mitochondrial growth relies on precise import of their resident proteins as well as transport and synthesis of phospholipids. Thus, protein import and lipid transport constitute the central processes of mitochondrial biogenesis and maintenance. The TOM complex in the outer mitochondrial membrane functions as an entry gate for most mitochondrial proteins. We found that the functional, preprotein-translocating mature trimeric TOM complex exchanges with a dimeric TOM complex form that lacks Tom22. This dynamic exchange between dimeric and trimeric forms provides the means for template-driven assembly of new subunits through their exchange for old defective subunits. The dimeric complex lacking Tom22 may be also important for possible lateral release of proteins with a helical transmembrane segment into the outer membrane. We are addressing the question of how the dynamic exchange between the dimeric and trimeric forms of the TOM complex is regulated in mitochondria. Mitochondrial functions strictly rely on the mitochondria-specific lipid compositions including cardiolipin and phosphatidylethanolamine, as well. Those phospholipids are synthesized from their precursor lipids such as phosphatidic acid and phosphatidylserine, which are made in the ER, and phosphatidylethanolamine made in the mitochondrial inner membrane also needs to be exported to the ER for conversion to other phospholipids including phosphatidylcholine. How phospholipid molecules with hydrophobic acyl chains can traverse aqueous compartments to shuttle between different membranes is a critical question concerning the mechanism of membrane biogenesis. At the moment, soluble lipid carrier proteins and inter-organelle membrane contact sites appear to provide efficient routes for phospholipid transfer between membranes. We are taking structural biology approaches to reveal the mechanisms of phospholipid transport processes involving mitochondria.
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