Mitochondrial membrane depolarization

Mitochondrial membrane depolarization refers to the dissipation of the electrochemical gradient (ΔΨm) across the inner mitochondrial membrane, a critical event linked to mitochondrial dysfunction. Depolarization can be a physiological signal, such as for mitophagy—the selective removal of damaged mitochondria—or a pathological event that leads to ATP depletion, increased ROS, and apoptosis. Various drugs exploit this process for therapeutic benefit in cancer and other diseases by inducing mitochondrial dysfunction and cell death. However, mitochondrial membrane depolarization itself is a phenomenon or cellular event rather than a druggable target in the conventional sense, and its modulation can carry significant risks due to the essential roles of mitochondria in healthy tissue homeostasis.

Other names

Mitochondrial depolarizationLoss of mitochondrial membrane potentialΔΨm loss

Disruption of mitochondrial bioenergetics (inhibition of electron transport chain complexes); Induction of mitochondrial permeability transition (mPT); Generation or modulation of ROS production; Decrease in ATP synthesis; Promotion of mitophagy through PINK1/Parkin pathway; Induction of apoptosis