| First Author | Ciavarra G | Year | 2010 |
| Journal | J Cell Biol | Volume | 191 |
| Issue | 2 | Pages | 291-301 |
| PubMed ID | 20937698 | Mgi Jnum | J:165519 |
| Mgi Id | MGI:4837595 | Doi | 10.1083/jcb.201005067 |
| Citation | Ciavarra G, et al. (2010) Rescue of myogenic defects in Rb-deficient cells by inhibition of autophagy or by hypoxia-induced glycolytic shift. J Cell Biol 191(2):291-301 |
| abstractText | The retinoblastoma tumor suppressor (pRb) is thought to orchestrate terminal differentiation by inhibiting cell proliferation and apoptosis and stimulating lineage-specific transcription factors. In this study, we show that in the absence of pRb, differentiating primary myoblasts fuse to form short myotubes that never twitch and degenerate via a nonapoptotic mechanism. The shortened myotubes exhibit an impaired mitochondrial network, mitochondrial perinuclear aggregation, autophagic degradation, and reduced adenosine triphosphate production. Bcl-2 and autophagy inhibitors restore mitochondrial function and rescue muscle degeneration, leading to formation of long, twitching myotubes that express normal levels of muscle-specific proteins and stably exit the cell cycle. A hypoxia-induced glycolytic switch also rescues the myogenic defect after either chronic or acute inactivation of Rb in a hypoxia-inducible factor-1 (HIF-1)-dependent manner. These results demonstrate that pRb is required to inhibit apoptosis in myoblasts and autophagy in myotubes but not to activate the differentiation program, and they also reveal a novel link between pRb and cell metabolism. |
