Function
While Humanin exerts neuroprotective and cytoprotective effects in models of Alzheimer’s disease, ischemia, and metabolic stress, reducing apoptosis and improving cell survival7136141, SS-31 improves mitochondrial bioenergetics, reduces oxidative stress, and shows protective effects in models of ischemia-reperfusion, neurodegeneration, and other mitochondrial disorders4637137.
Mechanism
While Humanin works as a mitochondrial-derived 24-amino-acid peptide that protects cells against diverse apoptotic insults by interacting with cell-surface cytokine receptor complexes and intracellular targets, thereby activating pro-survival STAT3 and other pathways7136141, SS-31 is a mitochondria-targeted tetrapeptide, d-Arg-dimethylTyr-Lys-Phe-NH2, that selectively binds cardiolipin in the inner mitochondrial membrane, stabilizing cristae structure, improving electron transport, and reducing ROS production4637137143.
Length and Sequence
Humanin is 24 amino acids long, whereas SS-31 is shorter as it has a length of 4 amino acids. Humanin is made up of a sequence of Methionine, Alanine, Proline, Arginine, Glycine, Phenylalanine, Serine, Cysteine, Leucine, Leucine, Leucine, Leucine, Leucine, Threonine, Serine, Glutamic acid, Isoleucine, Aspartic acid, Leucine, Proline, Valine, Lysine, Arginine, Arginine, Alanine. SS-31 is made up of a sequence of Arginine, dimethylTyr, Lysine, Phenylalanine.