SS-31

SS-31 belongs to the Szeto-Schiller peptides, designed with alternating aromatic and basic residues. That pattern gives the molecule an affinity for the inner mitochondrial membrane strong enough to concentrate it there by orders of magnitude — a targeting mechanism that is structural rather than receptor-mediated and needs no transport machinery.

Cardiolipin is found almost exclusively in the inner mitochondrial membrane, where it organises the folds — cristae — that hold the electron transport chain complexes in productive arrangement. When cardiolipin is disrupted, that architecture degrades and electron transport becomes less efficient and more prone to producing reactive oxygen species.

SS-31 binds cardiolipin, and the published mechanism is preservation of that architecture rather than antioxidant scavenging:

• Cristae morphology under electron microscopy

• Electron transport chain efficiency and ATP production

• Reactive oxygen species generation at the source rather than after release

• Primary mitochondrial myopathy, the clinical trial indication

• Ischaemia-reperfusion, heart failure and renal injury models

MOTS-c is the other mitochondrial peptide here, but acts as a signalling molecule from the mitochondrial genome rather than on membrane structure. NAD+ and Glutathione address mitochondrial function through cofactor and redox chemistry.