PMID- 20937698
OWN - NLM
STAT- MEDLINE
DCOM- 20110222
LR  - 20211020
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 191
IP  - 2
DP  - 2010 Oct 18
TI  - Rescue of myogenic defects in Rb-deficient cells by inhibition of autophagy or by 
      hypoxia-induced glycolytic shift.
PG  - 291-301
LID - 10.1083/jcb.201005067 [doi]
AB  - 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.
FAU - Ciavarra, Giovanni
AU  - Ciavarra G
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Zacksenhaus, Eldad
AU  - Zacksenhaus E
LA  - eng
PT  - Journal Article
DEP - 20101011
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Retinoblastoma Protein)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Autophagy/*physiology
MH  - Cell Differentiation
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Glycolysis/*physiology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/physiology
MH  - Mice
MH  - Mitochondria/metabolism/physiology/ultrastructure
MH  - Muscle Fibers, Skeletal/physiology
MH  - Myoblasts/cytology/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism/physiology
MH  - Retinoblastoma Protein/genetics/metabolism/*physiology
PMC - PMC2958467
EDAT- 2010/10/13 06:00
MHDA- 2011/02/23 06:00
PMCR- 2011/04/18
CRDT- 2010/10/13 06:00
PHST- 2010/10/13 06:00 [entrez]
PHST- 2010/10/13 06:00 [pubmed]
PHST- 2011/02/23 06:00 [medline]
PHST- 2011/04/18 00:00 [pmc-release]
AID - jcb.201005067 [pii]
AID - 201005067 [pii]
AID - 10.1083/jcb.201005067 [doi]
PST - ppublish
SO  - J Cell Biol. 2010 Oct 18;191(2):291-301. doi: 10.1083/jcb.201005067. Epub 2010 
      Oct 11.