Mitochondrial Signaling: Nitric Oxide Synthesis by Cytochrome c Oxidase and Its Oxygen Sensitivity Are Modulated by Adenine Nucleotides

ADP and ATP modulate mitochondrial cytochrome c oxidase–driven nitrite-to-nitric oxide (Cco/NO) activity, shifting oxygen sensitivity toward lower O2 with significant stimulation at 10 uM O2 and below.

• Why it matters: Regulation of Cco/NO in hypoxic signaling is unclear, and its quantitative importance versus other NO-producing pathways remains uncertain.
• What they did: Detergent-solubilized yeast and mouse brain mitochondria were assayed with 1 mM nitrite plus an ascorbate/TMPD/cytochrome c electron-donor system, testing ADP/ATP effects on oxygen sensitivity and isoforms Va versus Vb.
• The result: ADP shifted apparent oxygen sensitivity toward lower O2 and increased activity transiently after a hypoxic shift; ATP inhibited Va-containing Cco but strongly stimulated Vb-containing Cco under anoxia, indicating metabolic and isoform-dependent gating.

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