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Navdeep S. Chandel, PhDAssociate Professor
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Please visit the Chandel lab home page: http://www.chandellab.com/
The major function of mitochondria in cellular homeostasis has historically been the generation of energy through oxidative phosphorylation. However, we and others have demonstrated that mitochondria can serve as a signaling organelle. The projects in my lab are driven by the hypothesis that when cells encounter stress the mitochondria serve as key regulators of biological outcomes that include the induction of adaptive genes, cellular proliferation, senescence and death.
Hypoxic and oncogenic stress will be used to test our hypothesis. The microenvironment of stem cells and tumor cells is hypoxic. Failure to adapt to hypoxia results in tumor regression and loss of stem cell multipotency. Oncogenes are essential regulators of tumorigenesis including the conversion of stem cells to tumor cells. We hypothesize that the degree of hypoxic or oncogenic stress can release low levels of mitochondrial ROS to activate genes for cellular adaptation. Conversely, higher levels of mitochondrial ROS induce senescence. The degree of hypoxic or oncogenic stress is likely to regulate whether mitochondria provide substrates for lipid synthesis to allow cellular proliferation or commit to apoptosis through the release of cytochrome c during hypoxic or oncogenic stress. We are currently examining how mitochondria serve as a signaling organelle for stem cells and cancer.
Shroff EH, Snyder CM, Budinger GR, Jain M, Chew TL, Khuon S, Perlman H, Chandel NS. BH3 peptides induce mitochondrial fission and cell death independent of BAX/BAK. PLoS One. 2009 May 21;4(5):e5646.
Klimova TA, Bell EL, Shroff EH, Weinberg FD, Snyder CM, Dimri GP, Schumacker PT, Budinger GR, Chandel NS. Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS. FASEB J. 2009 Mar;23(3):783-94.
Emerling BM, Weinberg F, Liu JL, Mak TW, Chandel NS. PTEN regulates p300-dependent hypoxia-inducible factor 1 transcriptional activity through Forkhead transcription factor 3a (FOXO3a). Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2622-7.
Bell EL, Klimova TA, Eisenbart J, Moraes CT, Murphy MP, Budinger GR, Chandel NS. The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. J Cell Biol. 2007 Jun 18;177(6):1029-36.
Bell EL, Klimova TA, Eisenbart J, Schumacker PT, Chandel NS. Mitochondrial ROS trigger HIF-dependent extension of replicative lifespan during hypoxia. Mol Cell Biol. 2007 Aug;27(16):5737-45.
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View Publications by Navdeep Chandel listed in the National Library of Medicine (PubMed). |
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