Mitochondrial

Humanin is a 24-amino acid mitochondrial-derived peptide originally discovered in surviving neurons of Alzheimer's disease patients. It exerts neuroprotective effects primarily by inhibiting apoptosis via BAX binding, mitigating oxidative stress, preserving mitochondrial function, and counteracting neurotoxic insults like amyloid-beta in multiple disease models.

MOTS-c is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded within the 12S rRNA gene of mitochondrial DNA. Discovered in 2015, it functions as an 'exercise mimetic' through AMPK activation, NAD+ elevation, and sirtuin activation, with levels declining approximately 21% in elderly populations and higher levels observed in centenarians.

SHLP-2 is a 28-aa mitochondrial-derived peptide (MT-RNR2 encoded) with chaperone-like activity binding CXCR7 (EC50 ~0.97 µM). It restores OXPHOS complexes, reduces ROS, improves insulin sensitivity (50% higher glucose infusion rates), and activates POMC neurons for thermogenesis. A K4R variant provides Parkinson's protection.

SS-31 (elamipretide) is a mitochondria-targeting tetrapeptide that binds to cardiolipin in the inner mitochondrial membrane, stabilizing cristae structure, preventing cardiolipin peroxidation, and improving electron transport chain function. FDA-approved for Barth syndrome (FORZINITY), with ongoing trials for heart failure and mitochondrial diseases.