Mitochondrial electron transport chain complexes I and III (ETC Complexes I and III)

Mitochondrial electron transport chain (ETC) complexes I and III are essential multi-subunit enzymes located in the inner mitochondrial membrane that facilitate cellular respiration (Wikipedia, 2024). Complex I (NADH:ubiquinone oxidoreductase) and Complex III (ubiquinol-cytochrome c reductase) function sequentially to transfer electrons from NADH to cytochrome c, a process that drives the pumping of protons into the intermembrane space to establish the electrochemical gradient for ATP production (MDPI, 2021). These complexes are also the primary sites of reactive oxygen species (ROS) generation, making them central to both energy metabolism and oxidative stress signaling (NIH, 2021). In drug development, they are targeted to disrupt the bioenergetics of cancer cells (as 'mitocans') or to manage metabolic disorders, most notably through the Complex I inhibitor metformin (NIH, 2021; ResearchGate, 2021). However, their inhibition is associated with significant risks, including the development of lactic acidosis and neurodegenerative conditions, reflecting their vital role in maintaining cellular and systemic health (NIH, 2021; Wikipedia, 2021).

Other names

NADH:cytochrome c reductaseRespiratory chain complexes I and IIIComplex I and IIINADH dehydrogenase and Cytochrome bc1 complex

Inhibition of electron transfer within the mitochondrial respiratory chain, resulting in the depletion of ATP, accumulation of reactive oxygen species (ROS), and induction of the mitochondrial apoptotic pathway.