Function
While Humanin exerts neuroprotective and cytoprotective effects in models of Alzheimer’s disease, ischemia, and metabolic stress, reducing apoptosis and improving cell survival7136141, MOTS-c improves insulin sensitivity, enhances glycolysis, reduces oxidative stress, and shows protective effects in models of metabolic syndrome, aging, and ischemia-reperfusion injury8135146.
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, MOTS-c is a 16-amino-acid mitochondrial-derived peptide that translocates to the nucleus under metabolic stress and regulates glucose and lipid metabolism largely via activation of AMPK and modulation of mTOR and folate-cycle–linked pathways854140146.