Mansfield 2005 Cell Metab

Mansfield KD, Guzy RD, Pan Y, Young RM, Cash TP, Schumacker PT, Simon MC (2005) Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 1:393-9.

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Mansfield KD, Guzy RD, Pan Y, Young RM, Cash TP, Schumacker PT, Simon MC (2005) Cell Metab

Abstract: While cellular responses to low oxygen (O2) or hypoxia have been studied extensively, the precise identity of mammalian cellular O2 sensors remains controversial. Using murine embryonic cells lacking cytochrome c, and therefore mitochondrial activity, we show that mitochondrial reactive oxygen species (mtROS) are essential for proper O2 sensing and subsequent HIF-1α and HIF-2α stabilization at 1.5% O2. In the absence of this signal, HIF-α subunits continue to be degraded. Furthermore, exogenous treatment with H2O2 or severe O2 deprivation is sufficient to stabilize HIF-α even in the absence of cytochrome c and functional mitochondria. These results provide genetic evidence indicating that mtROS act upstream of prolyl hydroxylases in regulating HIF-1α and HIF-2α in this O2 sensing pathway. • Keywords: hypoxia, reactive oxygen species, HIF-1α, HIF-2α, anoxia • Bioblast editor: Sobotka O

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Stress:Oxidative stress;RONS, Hypoxia