MOTS-c: what the research shows

What MOTS-c is

MOTS-c stands for mitochondrial open reading frame of the 12S rRNA-c. It is a 16-amino-acid peptide encoded by a short open reading frame inside the mitochondrial gene for 12S ribosomal RNA, described in 2015. [1]

Mitochondria have their own small genome. MOTS-c was one of the first signalling peptides found to be encoded there, which is why it is called a mitochondrial-derived peptide. [1]

What the research covers

In the 2015 study, the primary target organ of MOTS-c appeared to be skeletal muscle. In cells it inhibited the folate cycle and the de novo purine synthesis linked to it, leading to activation of AMPK, an energy-sensing enzyme. In mice, MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance, as well as diet-induced obesity. [1]

A 2018 study showed that under metabolic stress, such as glucose restriction, MOTS-c moves into the cell nucleus in an AMPK-dependent way and regulates nuclear genes, including genes with antioxidant response elements, interacting with stress-responsive transcription factors such as NRF2. [2]

A 2021 study reported that MOTS-c improved physical performance in young, middle-aged and old mice, and that intermittent treatment started late in life increased physical capacity in mice. In humans, the same study found that exercise raises the body's own MOTS-c in skeletal muscle and in the circulation. [3]

What is not known

In the studies cited here, MOTS-c was given to cells and mice. The human data they report concern the body's own MOTS-c measured after exercise, not MOTS-c given from outside. [1] [3]

Status in sport

The World Anti-Doping Agency's 2026 Prohibited List names MOTS-c among the activators of AMP-activated protein kinase (AMPK), in the metabolic modulators of class S4, prohibited at all times, in and out of competition. [4]

Storage and stability in the lab

Peptides can degrade through chemical routes such as oxidation, deamidation and hydrolysis and through physical routes such as aggregation, and they are generally more stable in the dry state than in solution. [5]

Lyophilised vials are therefore normally kept cold, dry and away from light until they are reconstituted. The storage statement on the product page and on the batch certificate takes precedence.

How to check a batch

A useful certificate of analysis names the testing laboratory, the batch number printed on the vial, the test date and the methods used. Identity is usually confirmed by mass spectrometry, where the measured mass should match the expected molecular mass of the 16-amino-acid sequence, and purity is measured by HPLC.

Where the manufacturer supplies a batch report, we link it on the product page; products without one do not claim one.