Mitochondrial respiratory chain complex I and complex IV (Complex I/IV)

Mitochondrial complex I (NADH:ubiquinone oxidoreductase) and complex IV (cytochrome c oxidase) are essential components of the mitochondrial electron transport chain (ETC) located in the inner mitochondrial membrane [2, 7]. Complex I is the largest complex of the ETC, initiating the process by oxidizing NADH and transferring electrons to ubiquinone while pumping protons into the intermembrane space [7, 8]. Complex IV serves as the terminal enzyme, transferring electrons from cytochrome c to molecular oxygen to produce water, further contributing to the proton gradient used for ATP synthesis [11, 13]. Dysfunction in these complexes is a primary driver of mitochondrial diseases such as Leigh syndrome and Leber's hereditary optic neuropathy, and is implicated in the progression of neurodegenerative disorders like Parkinson's and Alzheimer's disease [2, 9, 12]. While complex I is a target for cancer therapies (e.g., IACS-010759) and metabolic drugs (e.g., metformin), its inhibition can lead to severe side effects like lactic acidosis and neurotoxicity [1, 3, 15]. Complex IV is notably inhibited by toxins such as cyanide and carbon monoxide, which halt cellular respiration [4, 13]. This entry is marked as incorrect because it combines two distinct protein complexes into a single target designation.

Other names

NADH:ubiquinone oxidoreductase and Cytochrome c oxidaseMitochondrial respiratory chain complexes I and IVComplex I and IVNADH dehydrogenase and Cytochrome c oxidase

Inhibition of electron transport, disruption of mitochondrial membrane potential, reduction of ATP synthesis, induction of oxidative stress, and induction of apoptosis.