Mitochondria can initiate cell death or activate genes that promote cell survival in response to low oxygen. The BCL-2 family of proteins regulate cell death in response to anoxia (0–0.5% O2). By contrast, under hypoxia (0.5–3% O2), mitochondrial oxidative stress activates hypoxia-inducible factors (HIFs) to promote cell survival. In this review, we discuss how mitochondria, BCL-2 proteins, and HIFs are crucial for cellular responses to low oxygen. Antioxid. Redox Signal. 11, 2673–2683.
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