Acute oxygen sensing by arterial chemoreceptors with a mutant mitochondrial complex I ND6 subunit lacking reverse electron transport.

Abstract

Carotid body glomus cells are essential for stimulating breathing in response to hypoxia. They contain specialized mitochondria in which hypoxia induces the accumulation of NADH and H₂O₂ that modulate membrane ion channel activity. We investigated whether hypoxia induces reverse electron transport (RET) at mitochondrial complex I (MCI). We studied glomus cells from mice with a mutation in ND6, a core protein of MCI, which maintain normal MCI NADH dehydrogenase activity but cannot catalyze RET. The ND6 mutation increases the propensity of MCI to deactivate, and glomus cells with deactivated MCI are insensitive to acute hypoxia. These findings further indicate that MCI function is necessary for glomus cell responsiveness to hypoxia, although MCI RET does not seem to be required for this process.