Mitochondrial Membrane
The double membrane system surrounding mitochondria — the outer membrane is permeable to small molecules while the inner membrane is highly selective and contains the electron transport chain. Cardiolipin in the inner membrane is the target of elamipretide, which stabilises its structure.
Technical Context
Outer mitochondrial membrane (OMM): permeable to small molecules (<5kDa) through VDAC (voltage-dependent anion channel/porin), site of BCL-2 family protein regulation of apoptosis. Intermembrane space: contains cytochrome c (released during apoptosis), pro-apoptotic factors. Inner mitochondrial membrane (IMM): highly impermeable (maintaining proton gradient essential for ATP synthesis), contains ETC complexes (I-IV) and ATP synthase (complex V), and is uniquely enriched in cardiolipin (approximately 20% of IMM lipid content). IMM cristae morphology: cristae junctions regulate metabolite diffusion between intermembrane space and intracristal space, affecting ETC efficiency. Elamipretide mechanism: the peptide's alternating aromatic-cationic structure (D-Arg-Dmt-Lys-Phe-NH2) enables selective accumulation on the IMM (approximately 5000-fold concentration vs cytoplasm), where it binds cardiolipin through electrostatic (cationic residues ↔ anionic cardiolipin headgroups) and hydrophobic (aromatic residues ↔ acyl chains) interactions, stabilising cristae structure and optimising ETC supercomplex assembly.