Peptide reference

MOTS-c

Mitochondrial ORF of the 12S rRNA type-c · a mitochondrial-derived peptide

A 16-amino-acid peptide encoded not by nuclear DNA but within the mitochondrial genome itself.

Residues

16

Molecular weight

~2174.6 g/mol

Encoded by

MT-RNR1 (12S rRNA)

Class

Mitochondrial-derived peptide

MRWQEMGYIFYPRKLR

Researched effects

Areas MOTS-c has been studied in. Every card carries an evidence-level badge.

Insulin sensitivity

Improved glucose disposal and reduced insulin resistance in diet-induced obese mice.

Rodent studies

Diet-induced obesity resistance

Reduced fat mass accumulation on a high-fat diet.

Rodent studies

AMPK activation

The central proposed signalling action underlying its metabolic effects.

In vitroRodent studies

Exercise response

Circulating and skeletal-muscle MOTS-c rise acutely with exercise in humans.

Human observational

Metabolic gene regulation

Translocates to the nucleus under metabolic stress and influences nuclear gene expression.

In vitro

Age-related decline

Circulating levels have been reported to fall with age.

Human observational

Longevity association

The m.1382A>C mitochondrial variant, which alters MOTS-c, has been associated with longevity in Japanese cohorts.

Human observational

Skeletal muscle function

Improved physical capacity in aged mice.

Rodent studies

Bone and metabolic markers

Early small human work exists but remains preliminary.

Early human trials

Sequence

Sixteen residues, N-terminus to C-terminus. Hover a node to inspect; filter by class to isolate.

Hover or focus a residue to inspect.

Sequence: MRWQEMGYIFYPRKLR. Sixteen residues in order: Met, Arg, Trp, Gln, Glu, Met, Gly, Tyr, Ile, Phe, Tyr, Pro, Arg, Lys, Leu, Arg.

Amino acid composition

How the sixteen positions distribute across twelve unique residues.

16residues
Arg× 3
Met× 2
Tyr× 2
Trp× 1
Gln× 1
Glu× 1
Gly× 1
Ile× 1
Phe× 1
Pro× 1
Lys× 1
Leu× 1
Arg18.75%

Arginine

count · 3pos · 2, 13, 16
Met12.5%

Methionine

count · 2pos · 1, 6
Tyr12.5%

Tyrosine

count · 2pos · 8, 11
Trp6.25%

Tryptophan

count · 1pos · 3
Gln6.25%

Glutamine

count · 1pos · 4
Glu6.25%

Glutamic acid

count · 1pos · 5
Gly6.25%

Glycine

count · 1pos · 7
Ile6.25%

Isoleucine

count · 1pos · 9
Phe6.25%

Phenylalanine

count · 1pos · 10
Pro6.25%

Proline

count · 1pos · 12
Lys6.25%

Lysine

count · 1pos · 14
Leu6.25%

Leucine

count · 1pos · 15

Structural properties

Four readouts characterising the chain.

Readout · 01

Net charge ≈ +4

Four basic residues (3× Arg, 1× Lys) against a single acidic Glu. The strong positive charge is relevant to membrane interaction and cellular uptake.

Readout · 02

Four aromatic residues

1× Trp, 2× Tyr and 1× Phe give strong absorbance at 280 nm, useful for analytical quantification.

Readout · 03

Two methionines

Susceptible to oxidation, a known handling and stability consideration for the peptide.

Readout · 04

No cysteine

No disulphide bonds; the peptide is short and largely unstructured in solution.

Proposed mechanisms

Pathways inferred from cell and rodent studies. Proposed / largely preclinical — not confirmed human mechanism.

Proposed · largely preclinical
MOTS-c
Folate–methionine cycle inhibition
AICAR accumulation
AMPK activation
GLUT4 translocation + fatty acid oxidation
Metabolic stress → nuclear translocation → binding at ATF1 → antioxidant & stress-response gene expression

Research & regulatory status

Not an approved medicine.

MOTS-c has no marketing authorisation as a drug in the US, UK or EU. It is sold only as a research chemical.

Non-approved substance in sport.

As an unapproved pharmacological agent it falls under WADA category S0, prohibited at all times.

Evidence is overwhelmingly preclinical.

The bulk of the literature is rodent and cell work from a small number of groups; human data is mostly observational, and long-term safety data in humans is absent.

The overwhelming majority of published evidence is preclinical, and long-term human safety data is absent.