Mitochondrial membrane (MM) (MM)

The mitochondrial membrane is a complex double-layered structure consisting of the outer mitochondrial membrane (OMM) and the highly folded inner mitochondrial membrane (IMM), which together define the functional compartments of the organelle [1, 14]. The IMM is the site of the electron transport chain and oxidative phosphorylation, housing essential proteins and the unique phospholipid cardiolipin, which is critical for maintaining cristae structure and respiratory supercomplex stability [3, 10]. Beyond energy production, these membranes regulate vital cellular processes including the intrinsic apoptotic pathway through the release of cytochrome c, calcium signaling, and the generation of reactive oxygen species (ROS) [4, 12]. In various pathologies, such as neurodegenerative diseases, heart failure, and primary mitochondrial myopathies, the structural integrity of the mitochondrial membrane is compromised, often characterized by cardiolipin peroxidation and the pathological opening of the mitochondrial permeability transition pore (MPTP) [5, 11]. Therapeutic strategies targeting the membrane include cardiolipin-protective peptides like elamipretide, which bind to the IMM to restore bioenergetic efficiency, and mitochondria-targeted antioxidants like MitoQ that accumulate at the membrane interface [2, 6]. Additionally, the membrane is a target for 'mitocans' in cancer therapy, which aim to disrupt mitochondrial stability to induce selective apoptosis in tumor cells [20, 23].

Other names

Inner mitochondrial membraneOuter mitochondrial membraneMitochondrial envelopeCristae membrane

Drugs targeting the mitochondrial membrane typically act by stabilizing membrane lipids like cardiolipin to improve bioenergetics, uncoupling the proton gradient to dissipate energy, inhibiting the mitochondrial permeability transition pore (MPTP) to prevent apoptosis, or delivering targeted antioxidants to the matrix [1, 2, 5].