Mitochondrial-derived peptide (MDP)

Mitochondria carry their own small genome, long thought to encode only the components of the energy-producing machinery. In the 2000s and 2010s several short open reading frames were found hidden inside mitochondrial genes, encoding peptides that mitochondria release as signals to the rest of the cell and, via the blood, to the rest of the body. These are the mitochondrial-derived peptides. Humanin was the first; MOTS-c, sixteen residues encoded within the 12S ribosomal RNA gene, was described in 2015.

MOTS-c is the one that reached research supply. In mice it activates AMP-activated protein kinase, the cell's energy sensor, improves insulin sensitivity and increases exercise capacity, and its levels in human blood fall with age and rise with exercise. A pharmaceutical analogue completed early human trials before its developer changed direction. The MOTS-c profile sets out what is animal data, what is human observational data, and what is still absent.

The category matters because it reframes mitochondria from power plants into signalling organelles, and because it is where several longevity-oriented compounds, including the non-peptide NAD+ and the small molecule SLU-PP-332, converge on the same cellular pathways.