SS-31

The defining feature of SS-31 is where it goes. Most peptides distribute broadly after injection. SS-31 carries a net positive charge that draws it electrostatically across the mitochondrial membrane potential — the steepest electrical gradient in biology — concentrating it up to 1000-fold inside the organelle where it is needed most. Once there, SS-31 binds **cardiolipin**, a dimeric phospholipid found almost exclusively in the inner mitochondrial membrane (IMM). Cardiolipin is not a passive structural molecule — it is the scaffold around which electron transport chain complexes I, III, and IV are assembled into supercomplexes. When cardiolipin oxidises due to reactive oxygen species, ischaemia, or age-related membrane deterioration, these supercomplexes disassemble, electron transfer becomes inefficient, and ATP production collapses. By binding and stabilising cardiolipin, SS-31 prevents this cascade. ETC architecture is preserved. Proton gradient is maintained. ATP production continues under conditions that would otherwise cause energetic failure. The downstream effects are broad. By preserving ETC efficiency, SS-31 reduces **electron leak** — the point source of mitochondrial superoxide and the ROS cascade that damages mitochondrial DNA, proteins, and membranes. This is qualitatively different from exogenous antioxidants: instead of mopping up ROS after they form, SS-31 reduces the structural conditions that generate them. It also inhibits **cytochrome c release** from the IMM — a key initiating step in the intrinsic apoptotic cascade — providing cellular protection in ischaemic tissue. In preclinical sarcopenia models, SS-31 has additionally been shown to promote mitochondrial biogenesis via **PGC-1α upregulation**, partially restoring the mitochondrial density that declines with ageing.