MOTS-c Peptide: The Signal Hidden in Mitochondrial DNA

For decades, mitochondria were described as the cell’s power plants and little more. MOTS-c is part of why that view changed. It is a 16-amino-acid peptide whose code sits in mitochondrial DNA, and it appears to act as a signal, not just a by-product of energy production.

A peptide from an unexpected place.

Almost all of a cell’s proteins are encoded in the nucleus. Mitochondria keep a small genome of their own, long thought to hold nothing more than 13 protein genes and the RNAs needed to build them.

In 2015, Changhan Lee and colleagues at the University of Southern California reported that a short open reading frame tucked inside the mitochondrial 12S rRNA gene produces a working peptide. They named it MOTS-c: Mitochondrial Open reading frame of the Twelve S rRNA type-c. It joined a small family of mitochondrial-derived peptides that also includes humanin, found earlier in the 16S rRNA region.

What the research looks at.

Most MOTS-c work is metabolic:

• AMPK and the folate cycle. Early studies linked MOTS-c to the folate cycle and to activation of AMPK, a key cellular energy sensor.
• Insulin sensitivity. Mouse studies looked at insulin sensitivity in diet-induced obesity models.
• Muscle and exercise. Work has examined glucose uptake in skeletal muscle and how MOTS-c levels shift with exercise and age.
• Stress signalling. Under cellular stress, MOTS-c has been reported to move into the nucleus and influence gene expression, a two-way conversation between mitochondria and nucleus.

Nearly all of this comes from cell and animal studies. It describes a promising line of research, not established effects in people.

Related research compounds.

MOTS-c often sits alongside other compounds in metabolic and ageing research. NAD+ is the coenzyme at the centre of cellular energy metabolism. 5-Amino-1MQ blocks the enzyme NNMT, which consumes NAD+ precursors. SLU-PP-332 activates receptors that drive mitochondrial energy genes in muscle. For more on that last group, see small molecules in peptide research.

Formats and documentation.

We supply MOTS-c as lyophilized powder in 10 mg and 40 mg vials. Every lot is third-party HPLC tested, with certificates in our COA library. See how to reconstitute peptides for preparation.

Questions.

What does MOTS-c stand for?

Mitochondrial Open reading frame of the Twelve S rRNA type-c.

Is MOTS-c made by mitochondria?

The natural peptide is encoded in mitochondrial DNA. Research material is a synthetic copy of the same 16-residue sequence.

Is MOTS-c related to humanin?

Both are mitochondrial-derived peptides. Humanin comes from the 16S rRNA region, MOTS-c from the 12S region.

Is MOTS-c approved for human use?

No. It is sold for laboratory research only.

For laboratory research use only. Not for human or veterinary use. Nothing in this article is medical advice or guidance on human use.