| Mitochondrial Complex IV (Cytochrome c Oxidase; COX) — Terminal enzyme complex of the mitochondrial electron transport chain. Complex IV accepts electrons from reduced cytochrome c and transfers them to molecular oxygen, reducing O2 to water. This electron transfer is coupled to proton pumping across the inner mitochondrial membrane and contributes to generation of the proton-motive force used for ATP synthesis.
Typical modulation in cancer: Context-dependent. ↑ Complex IV activity can support oxidative phosphorylation, ATP production, and survival in tumors dependent on mitochondrial respiration. Conversely, inhibition or dysfunction of Complex IV can reduce oxygen consumption and ATP production, increase mitochondrial stress, alter ROS generation, and promote cell death. Some cancer cells compensate for Complex IV inhibition by increasing glycolysis.
Typical modulation in Alzheimer’s disease: ↓ Complex IV activity is commonly associated with mitochondrial dysfunction, impaired oxidative phosphorylation, reduced ATP production, and increased oxidative stress in neurodegenerative disease. Reduced cytochrome c oxidase activity has been reported in Alzheimer’s disease brain and peripheral tissues.
Typical mechanistic relationship: Cytochrome c oxidation → electron transfer to O2 → H2O formation → proton pumping ↑ → mitochondrial membrane potential maintained → ATP synthesis supported.
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