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Publication : RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis.

First Author  Chen W Year  2014
Journal  Cell Death Differ Volume  21
Issue  7 Pages  1061-70
PubMed ID  24583643 Mgi Jnum  J:229499
Mgi Id  MGI:5752124 Doi  10.1038/cdd.2014.25
Citation  Chen W, et al. (2014) RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1alpha-mediated mitochondrial oxidative phosphorylation and glycolysis. Cell Death Differ 21(7):1061-70
abstractText  Aerobic glycolysis or the Warburg effect contributes to cancer cell proliferation; however, how this glucose metabolism pathway is precisely regulated remains elusive. Here we show that receptor-interacting protein 1 (RIP1), a cell death and survival signaling factor, regulates mitochondrial oxidative phosphorylation and aerobic glycolysis. Loss of RIP1 in lung cancer cells suppressed peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) expression, impairing mitochondrial oxidative phosphorylation and accelerating glycolysis, resulting in spontaneous DNA damage and p53-mediated cell proliferation inhibition. Thus, although aerobic glycolysis within a certain range favors cancer cell proliferation, excessive glycolysis causes cytostasis. Our data suggest that maintenance of glycolysis by RIP1 is pivotal to cancer cell energy homeostasis and DNA integrity and may be exploited for use in anticancer therapy.
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