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Sci. Signal., 3 July 2012
Vol. 5, Issue 231, p. ra47
Mitochondria for Transcription
A key response to reduced oxygen tension, a condition referred to as hypoxia, involves the hypoxia-inducible factor (HIF) family of transcription factors. During hypoxia, HIF-1α translocates to the nucleus to activate genes involved in adapting to oxygen deprivation. Al-Mehdi et al. showed that the transcriptional response to hypoxia was accompanied by the subcellular redistribution of mitochondria around the nucleus. Reactive oxygen species produced by the redistributed mitochondria caused oxidative modification of the promoter regions of HIF-1 target genes, such as that encoding vascular endothelial growth factor (VEGF). The introduction of oxidative modifications in these promoters enhanced HIF-1α association and gene expression. Because the presence of hypoxia in solid tumors is an indicator of poor prognosis, understanding the details of the transcriptional response to hypoxia may provide new targets for the therapeutic treatment of solid tumors.
Citation: A.-B. Al-Mehdi, V. M. Pastukh, B. M. Swiger, D. J. Reed, M. R. Patel, G. C. Bardwell, V. V. Pastukh, M. F. Alexeyev, M. N. Gillespie, Perinuclear Mitochondrial Clustering Creates an Oxidant-Rich Nuclear Domain Required for Hypoxia-Induced Transcription. Sci. Signal.5, ra47 (2012).