Mitochondrial Bioenergetics: The Crucial Role of Cardiolipin-Targeted Peptides

Mitochondria are often designated as the powerhouses of eukaryotic cells, generating ATP via oxidative phosphorylation across the electron transport chain (ETC). However, mitochondrial dysfunction is a primary hallmark of cellular senescence and metabolic stress. ### Cardiolipin Interaction Cardiolipin is a unique dimeric phospholipid localized exclusively in the inner mitochondrial membrane (IMM). It is vital for maintaining the structural integrity of cristae and organizing respiratory supercomplexes. During oxidative stress, lipid peroxidation of cardiolipin destabilizes the ETC, leading to electron leakage and elevated ROS production. ### Mechanism of Targeted PeptidesCompounds such as SS-31 selectively concentrate in the IMM by binding electrostatically to cardiolipin. This prevents cytochrome c from peroxidase activity and maintains optimal membrane curvature, restoring robust ATP synthesis without altering basal oxygen consumption.