The molecule and where it comes from
MOTS-c is a short, simple peptide: a single chain of 16 amino acids.
Sixteen residues read out of a ribosomal RNA gene
MOTS-c is a short, simple peptide: a single chain of 16 amino acids. Its published sequence contains no cysteine, so it has no disulfide bonds. What makes it remarkable is not its shape but its address. It is encoded by a small open reading frame nested inside the mitochondrial 12S rRNA gene (MT-RNR1), a region that classical genetics said only made ribosomal RNA.
This unit reads the molecule and its genomic origin together: the sequence and the one residue (position 14) that carries a famous polymorphism, how a peptide can be hidden inside an rRNA gene, and why the mitochondrial genetic code matters. The chemistry here is settled fact, which makes it a clean place to practice separating what is known from what is merely claimed.
Key terms
The 16-residue chain
MOTS-c is one short chain of 16 building blocks (amino acids): Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg, as FDA’s 2026 review prints it. There is no cysteine in it, so no disulfide (sulfur-to-sulfur) bridge. The one feature worth memorizing is position 14: the lysine there becomes glutamine in carriers of a single mtDNA change, m.1382A>C (the K14Q variant), which is associated with type 2 diabetes in men and with muscle fiber composition. That one-building-block difference (a single residue) is the hook for the human-genetics story told later. Tap the regions to explore the chain.
Sixteen residues is short for a signaling molecule, and no fetched source in this course reports a solved structure for it. What the record does say is that the molecular target is unknown: FDA reviewers noted in 2026 that although AMPK-dependent signaling appears to contribute to its effects, the molecular targets remain unidentified, which makes it hard to predict which organs MOTS-c would even affect.