Mitochondrial complex III: an essential component of universal oxygen sensing machinery?

Oxygen is necessary for the survival of mammalian cells. In order to maintain adequate cellular oxygenation, mammals have evolved multiple acute and long-term adaptive responses to hypoxia. These include hypoxic increases in erythropoiesis, pulmonary vasoconstriction and carotid body neurosecretion. Collectively, these responses help maintain oxygen homeostasis as oxygen levels remain scarce. There are multiple effectors proposed to underlie these diverse responses to hypoxia including PHD2, AMPK, NADPH oxidases, and mitochondrial complex III. Here I propose a model wherein complex III is integral to oxygen sensing in regulating diverse response to hypoxia.