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Humanin (HN) is a natural short mitochondrial polypeptide with antiapoptotic and neuroprotective effects. Humanin protects cells against various diseases, including oxidative stress and cytotoxicity induced by various stimuli with broad-spectrum activity on the pancreas, brain, testis, and heart.

Humanin (HN/MTRNR2) has also been cloned as a BAX partner that could suppress apoptosis caused by staurosporine, serum deprivation, or u.v. irradiation. Using co-immunoprecipitation experiments, humanin specifically bound to BAX, tBID, and BimEL (BCL2L11), but not other BCL2 family proteins such as BCL2 and BCL-B (BCL2L10). Furthermore, the anti-apoptotic effect of humanin was specific to BAX-dependent apoptosis, as apoptosis by a BAX-independent stimulus, such as the use of tumor necrosis factor, was not suppressed. Humanin also interacts with insulin-like growth factor-binding protein 3 (IGFBP3), where it can block IGFBP3-induced apoptosis in glial cell lines but not in neuronal cell lines or primary neurons[1].

Humanin is 24-amino acid mitochondria-associated peptide that is involved in numerous biological processes including apoptosis, cell survival, substrate metabolism, inflammatory response, and response to stressors such as oxidative stress, ischemia, and starvation. Humanin exhibits protective effects against cellular apoptosis. Apparently it inhibits BAX translocation to the mitochondrial outer membrane.

[1] Kelvin Yen. “The emerging role of the mitochondrial-derived peptide humanin in stress resistance.” Journal of molecular endocrinology 50 1 (2013): R11-9.