MOTS-c is encoded by mitochondrial DNA, not the nuclear genome. Research into what that means is still developing.
MOTS-C
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial genome, specifically within the 12S ribosomal RNA gene, rather than in nuclear DNA. It belongs to a small class known as mitochondrial-derived peptides, which were only characterised in the last two decades.
The interesting part is the address, not just the molecule. Mitochondria were long treated as organelles that receive instructions from the nucleus. The identification of peptides encoded in mitochondrial DNA that appear to act elsewhere in the cell suggested signalling running in the other direction, which is why this class attracted attention well beyond metabolic research.
The peptide was described in Cell Metabolism in 2015 by Lee and colleagues, who examined its relationship to metabolic homeostasis in cell and rodent models. Subsequent work has looked at exercise physiology, ageing, and circulating concentrations across populations. The human literature remains considerably thinner than the preclinical literature.