Peptide · Research Monograph · Mitochondrial-derived 16-amino acid peptide

MOTS-c

Mitochondrial Metabolism Studies

MOTS-c is a short peptide, 16 amino acids long. What makes it unusual is where the instructions for it are stored. They sit inside mitochondrial DNA rather than in the cell nucleus. Studies have measured how it activates AMPK, a pathway that senses cellular energy levels, and how it affects glucose use in muscle models. Only a handful of peptides like it have been found, all within the past twenty years.

Formula
C101H152N28O22S2
Mol. weight
2174.64 Da
Length
16 residues
Size
10mg, 30mg, 50mg
View product & pricing → Lot records & COAs

For laboratory research use only - not for human or animal use

MOTS-c vial from the Eon Peptides research catalog
Fig. 1MOTS-c · 10mg / 30mg / 50mg · catalog photograph
Available in the Eon catalog - MOTS-c from $40.00 View certificate of analysisILS Laboratories · 99.86% purity · Lot MOTSC-101926-10

Molecular data

Molecular formulaC101H152N28O22S2
Molecular weight2174.64 Da
SequenceMRWQEMGYIFYPRKLR
Sequence length16 residues
Physical formLyophilized Powder
Available sizes10mg, 30mg, 50mg

The sequence

MOTS-c is published as a 16-residue sequence. It is set below in reading order, ten residues to a row, numbered from the N-terminus. Every position is a standard L-amino acid.

Fig. 2Primary sequence of MOTS-c as published in the catalogue specification, 16 residues, numbered from the N-terminus. A filled square marks a residue with no one-letter code.

One-letterMRWQEMGYIFYPRKLR

Residues
16
Published as
One-letter code
Termini
Not stated in the specification

How it works

  1. AMPK Activation

    AMP-Activated Protein Kinase Signaling

    MOTS-c activates AMP-activated protein kinase (AMPK) in skeletal muscle, adipose tissue, and liver. AMPK is a master metabolic sensor that responds to cellular energy status. MOTS-c-induced AMPK activation in preclinical models was associated with increased glucose uptake, fatty acid oxidation, and mitochondrial biogenesis signaling.

    • Direct AMPK phosphorylation (Thr172) in skeletal muscle
    • Downstream activation of PGC-1α and mitochondrial biogenesis
    • GLUT4 translocation and glucose uptake measured
  2. mtDNA Origin

    Mitochondria-to-Nucleus Retrograde Signaling

    MOTS-c is encoded within the 12S rRNA gene of the mitochondrial genome - a discovery that established mitochondria as an endocrine organ capable of producing bioactive peptides. Under metabolic stress, MOTS-c translocates from mitochondria to the nucleus where it acts as a transcriptional regulator, modulating antioxidant response element (ARE) gene expression.

    • Encoded in mitochondrial DNA (12S rRNA gene region)
    • Nuclear translocation under metabolic stress conditions
    • Modulates ARE-driven antioxidant gene expression
  3. Exercise Mimetic

    Metabolic Homeostasis & Exercise Signaling

    MOTS-c levels rise in response to exercise, and in mouse models several exercise-associated metabolic measures were recorded following exogenous MOTS-c - insulin sensitivity, adiposity and endurance - including in sedentary animals. It also acts on the folate cycle and purine synthesis under stress, redirecting metabolic flux.

    • Endogenous levels increase with aerobic exercise
    • Insulin sensitivity studied in rodent metabolic models
    • Inhibits AICAR-independent AMPK activation via folate cycle

What the research shows

  1. Metabolic Research

    Insulin Sensitivity Models

    In high-fat diet mouse models, insulin sensitivity, fat accumulation and glucose tolerance were measured following MOTS-c administration, with skeletal muscle AMPK activation as the proposed mediator.

  2. Aging Biology

    Age-Related Metabolic Decline

    Circulating MOTS-c levels decline with age in both humans and rodents. In aged mouse models, physical performance and metabolic flexibility measures were recorded following exogenous MOTS-c, and are studied in the context of mitochondrial-nuclear communication.

  3. Exercise Biology

    Exercise Mimicry

    Circulating MOTS-c rises with aerobic exercise in humans. In sedentary mouse models, energy metabolism, mitochondrial biogenesis markers and endurance measures were recorded following exogenous MOTS-c.

  4. Population Genetics

    mtDNA Variation & Ageing Cohorts

    Population studies identified MOTS-c variants (particularly R150Q) enriched in elderly Japanese cohorts. Sequence variation correlates with metabolic markers, which is why mitochondrial peptide biology is studied in ageing research.

Specification

Full NameMitochondrial Open Reading Frame of the 12S rRNA-c
SequenceMRWQEMGYIFYPRKLR
Amino Acids16 residues
Molecular Weight2174.6 Da
Gene OriginMitochondrial 12S rRNA (mt-RNR1)
Primary TargetAMPK activation; folate cycle; nuclear ARE pathways
FormLyophilized powder (5mg)
Purity≥99% (HPLC verified)
TestingThird-party HPLC, Mass Spec, Endotoxin
Storage-20°C for long-term stability
SolubilityWater-soluble
COAIncluded with every order

How it's tested

Every lot of MOTS-c released to the catalog carries a third-party certificate of analysis. 7 documented lots are on file for this compound, with reported HPLC purity from 99.52% to 99.90% (mean 99.74%), issued by ILS Laboratories, Freedom Diagnostics and Accurate Test Labs. 5 of 7 certificates record identity as confirmed.

Documented lots
7
Reported purity
99.52% to 99.90%
Mean purity
99.74%
Issuing labs
ILS Laboratories, Freedom Diagnostics, Accurate Test Labs
100% 99% 98% 99.74% Lot Whol2605120007 · 2026-05-11 · 99.59%Lot Whol2605130124 · 2026-05-13 · 99.76%Lot MC-092426-10 · 2026-09-25 · 99.90%Lot MOTSC-092126-10 · 2026-09-27 · 99.52%Lot MOTSC-101926-10 · 2026-10-19 · 99.86%Lot MOTSC-101926-40 · 2026-10-19 · 99.78% 2026-05-11 2026-10-19
Fig. 3Reported HPLC purity of all 6 documented lots, plotted on the date each certificate was issued, 2026-05-11 to 2026-10-19. One point is one certificate; the points are not joined because the archive records lots, not a continuous measurement. Vertical window 98.00% to 100%, dashed rule is the mean at 99.74%.

All certificates in the COA library →

Frequently asked questions

What is MOTS-c and where does it come from?

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial genome - specifically in the 12S ribosomal RNA gene. Discovered in 2015 by researchers at USC led by Dr. Changhan David Lee, it was one of the first identified mitochondrial-derived peptides (MDPs). Unlike most mitochondrial proteins, MOTS-c is translated from a small open reading frame within non-coding RNA, establishing a new category of regulatory peptides originating from the organelle long considered only a metabolic powerhouse.

How does MOTS-c act as an exercise mimetic?

Circulating MOTS-c levels in humans and rodents rise in response to aerobic exercise. MOTS-c activates AMPK - the same energy sensor activated by exercise - in skeletal muscle and other metabolic tissues. In preclinical studies, sedentary mice given exogenous MOTS-c showed metabolic changes overlapping those of exercise training: insulin sensitivity, fatty acid oxidation, mitochondrial biogenesis markers and endurance were all measured. This overlap is why MOTS-c is studied in metabolic biology.

What is the relationship between MOTS-c and aging?

MOTS-c levels decline with age in both humans and rodents, inversely correlating with age-related metabolic markers. Population genetic studies identified a MOTS-c variant (R150Q, also called K14Q in some notation systems) enriched in elderly Japanese men. In aged mouse models, physical performance and metabolic flexibility measures were recorded following exogenous MOTS-c, which is why it is studied in ageing biology.

How does MOTS-c activate AMPK without exercise?

MOTS-c activates AMPK through an indirect mechanism involving the folate cycle. Under metabolic stress, MOTS-c inhibits the enzyme MTHFR (methylenetetrahydrofolate reductase) in the folate-methionine cycle. This disrupts purine nucleotide biosynthesis, causing accumulation of ZMP (5-aminoimidazole-4-carboxamide ribonucleoside monophosphate) - a known AMPK activator. This AICAR-independent pathway for AMPK activation is one of the key mechanistic findings distinguishing MOTS-c from other metabolic peptides.

Are there human studies on MOTS-c?

Human research on MOTS-c primarily consists of observational and correlational studies measuring circulating MOTS-c levels in various populations. These have shown associations between MOTS-c levels and: exercise status, aging, insulin resistance, and cardiovascular disease. Human genetic studies have identified longevity-associated MOTS-c variants. However, no randomized controlled trials of exogenous MOTS-c administration in humans have been completed or published as of 2024.

How should MOTS-c be stored and handled for research?

Store lyophilized MOTS-c at -20°C, protected from light and humidity, and minimize freeze-thaw cycles. MOTS-c is water-soluble, making it suitable for aqueous research systems. For cell culture experiments, filter-sterilize laboratory solutions before use. Always consult published protocols for concentration-specific guidance.

Other entries in this volume that bear on MOTS-c, with the reason each one is listed.

For laboratory research use only. Not a drug, supplement, or medical product; not for human or animal use. All findings referenced are from published preclinical/laboratory research.