Mitochondrial inner membrane potential (ΔΨm) and lipid bilayer (ΔΨm/IMM)

The mitochondrial inner membrane potential (ΔΨm) and the lipid bilayer are essential for cellular bioenergetics and homeostasis. The ΔΨm is an electrochemical gradient generated by the electron transport chain, which drives the synthesis of ATP through oxidative phosphorylation (StatPearls, 2023). The inner mitochondrial membrane (IMM) lipid bilayer is uniquely composed of cardiolipin, a phospholipid that organizes respiratory complexes into supercomplexes and maintains membrane curvature (PubMed, PMID: 28213318). Dysregulation of the ΔΨm or damage to the lipid bilayer is a hallmark of various conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer, often leading to the release of pro-apoptotic factors like cytochrome c (NIH, 2021). Therapeutic interventions include mitochondrial uncouplers like 2,4-dinitrophenol, which reduce the ΔΨm to increase metabolic rate, and membrane-stabilizing agents like elamipretide, which bind to cardiolipin to restore mitochondrial efficiency (Journal of Clinical Investigation, 2018). Additionally, the negative charge of the ΔΨm is frequently exploited to deliver mitochondria-targeted antioxidants, such as MitoQ, directly into the matrix.

Other names

Inner mitochondrial membraneMitochondrial membrane potentialΔΨmIMMMitochondrial lipid bilayer

Pharmacological modulation involves the dissipation of the proton gradient via uncoupling, stabilization of cardiolipin-rich membrane domains, or the use of the electrochemical gradient for the sequestration of mitochondria-targeted molecules.