Sci. STKE, 11 March 2003
Organellar Signals c-Src Promotes Mitochondrial Function
Nonreceptor tyrosine kinases can be associated with various internal membranes, however their functions are best understood only at the plasma membrane. Miyazaki et al. investigated the role of c-Src associated with the inner mitochondrial membrane and the relevance of mitochondrial c-Src for osteoclast function--osteoclasts resorb bone. Subunit II of cytochrome oxidase (CoxII) was phosphorylated by c-Src and c-Src deficiency resulted in decreased Cox activity. Enhanced c-Src function through expression of a kinase-inactive Csk (phosphorylation by Csk inhibits c-Src activity) increased Cox activity in cultured osteoclasts, whereas inhibition of c-Src by expression of kinase-inactive c-Src or wild-type Csk decreased Cox activity. Enhanced c-Src activity in kinase-inactive Csk transfected cells antagonized the ability of calcitonin to decrease Cox activity and bone resolving activity in osteoclasts. Thus, with osteoclasts as a model, a role for mitochondrial c-Src appears to be phosphorylation of Cox subunits resulting in enhanced Cox activity. In osteoclasts, this Cox activity is essential for proper bone resorption activity. What signals regulate mitochondrial c-Src activity remain to be elucidated.
Citation: c-Src Promotes Mitochondrial Function. Sci. STKE 2003, tw106 (2003).
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