Category

Mitochondrial Peptides

Two different kinds of molecule are filed together here, and the distinction is the first thing to settle: peptides that the mitochondrial genome itself encodes, and synthetic peptides designed to accumulate in the inner membrane. Both are read against mitochondrial endpoints, but they do not act alike and are rarely substituted for one another.

Humanin and MOTS-c are the encoded ones. Humanin is 24 residues, 2687.27 g/mol, read from the 16S rRNA region of mitochondrial DNA, and its literature is cytoprotective — apoptosis signalling, neuronal survival, endothelial and metabolic models. MOTS-c is 16 residues, 2174.55 g/mol, from the 12S rRNA region, and behaves as a metabolic signal instead: AMPK activation, glucose and lipid handling, one-carbon metabolism, and the exercise-physiology work. They share an origin and very little else, which is why a design usually commits to one of them rather than both.

SS-31 is the designed one. Also catalogued as elamipretide, MTP-131 and Bendavia, it is a four-residue Szeto–Schiller aromatic-cationic peptide — D-Arg-Dmt-Lys-Phe-NH2, 639.80 g/mol, where Dmt is 2',6'-dimethyl-L-tyrosine — roughly a quarter the mass of Humanin. Its alternating cationic and aromatic residues carry it across the inner membrane without a transporter, and once there it binds cardiolipin; the cristae-structure, reactive-oxygen-species and ischaemia–reperfusion work all follows from that binding rather than from a receptor. The D-arginine and the unnatural tyrosine also make it unusually peptidase-resistant for its size. Fills: Humanin at 5 and 10 mg, MOTS-c from 5 to 40 mg, SS-31 from 10 to 50 mg, all lyophilized, plus MOTS-c as 5 mg oral capsules — the only oral route on the shelf, and studied as much for peptide stability as for signalling.