| First Author | Miyazaki T | Year | 2003 |
| Journal | J Cell Biol | Volume | 160 |
| Issue | 5 | Pages | 709-18 |
| PubMed ID | 12615910 | Mgi Jnum | J:281184 |
| Mgi Id | MGI:6377732 | Doi | 10.1083/jcb.200209098 |
| Citation | Miyazaki T, et al. (2003) Regulation of cytochrome c oxidase activity by c-Src in osteoclasts. J Cell Biol 160(5):709-18 |
| abstractText | The function of the nonreceptor tyrosine kinase c-Src as a plasma membrane-associated molecular effector of a variety of extracellular stimuli is well known. Here, we show that c-Src is also present within mitochondria, where it phosphorylates cytochrome c oxidase (Cox). Deleting the c-src gene reduces Cox activity, and this inhibitory effect is restored by expressing exogenous c-Src. Furthermore, reducing endogenous Src kinase activity down-regulates Cox activity, whereas activating Src has the opposite effect. Src-induced Cox activity is required for normal function of cells that require high levels of ATP, such as mitochondria-rich osteoclasts. The peptide hormone calcitonin, which inhibits osteoclast function, also down-regulates Cox activity. Increasing Src kinase activity prevented the inhibitory effect of calcitonin on Cox activity and osteoclast function. These results suggest that c-Src plays a previously unrecognized role in maintaining cellular energy stores by activating Cox in mitochondria. |
