Mitochondrial inner membrane potential (Δψm)

Mitochondrial inner membrane potential (Δψm) is the electrochemical gradient generated by the electron transport chain across the inner mitochondrial membrane, which is essential for ATP synthesis and mitochondrial homeostasis (Galluzzi et al., 2012). In senescent cells, Δψm is frequently altered, often exhibiting depolarization or instability as part of the senescence-associated mitochondrial dysfunction (SAMD) phenotype (Passos et al., 2007). This dysfunction is a key driver of the pro-inflammatory senescence-associated secretory phenotype (SASP) and increased reactive oxygen species (ROS) production (Wiley et al., 2016). While Δψm is a physiological state rather than a discrete molecular target like a receptor, it serves as a critical biomarker for identifying senescent cells and evaluating the efficacy of senolytic and senomorphic therapies (Korneeva et al., 2021). Drugs such as CCCP or metformin can modulate this potential, though achieving the specificity required to target senescent cells without harming healthy tissue remains a significant therapeutic challenge (Vial et al., 2019). Targeting the metabolic vulnerabilities associated with Δψm changes is a burgeoning strategy in geroscience to treat age-related diseases (Lagouge and Larsson, 2013).

Other names

Mitochondrial membrane potentialΔψmMMPMitochondrial electrochemical gradientMitochondrial proton gradient

Modulation of the mitochondrial electrochemical gradient through protonophore uncoupling, electron transport chain inhibition, or ATP synthase modulation.