Editors' ChoiceOrganellar Signals

c-Src Promotes Mitochondrial Function

Science's STKE  11 Mar 2003:
Vol. 2003, Issue 173, pp. tw106-TW106
DOI: 10.1126/stke.2003.173.tw106

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.

T. Miyazaki, L. Neff, S. Tanaka, W. C. Horne, R. Baron, Regulation of cytochrome c oxidase activity by c-Src in osteoclasts. J. Cell Biol. 160, 709-718 (2003). [Abstract] [Full Text]