P Palthera
Signalling Peptides

MOTS-c

Mitochondrial open reading frame of the twelve S rRNA-c

MOTS-c is a 16- peptide encoded within the mitochondrial 12S rRNA open reading frame, discovered in 2015. It has been studied in metabolic homeostasis, insulin resistance, and skeletal muscle research. All cited primary studies on this profile are (mouse and cell models).

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Signalling Peptides
Classification
Mitochondrial-derived peptide (mitochondrial 12S rRNA open reading frame product)
Research stage
Active preclinical literature (mouse and cell models); no controlled human clinical trials at time of writing
Sequence
Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
Molecular weight
2174.6 Da

Snapshot

Key takeaways

A three-bullet snapshot before reading the full dossier.

  1. 01

    Mitochondrially-encoded 16- peptide, distinct from nuclear-encoded peptides.

  2. 02

    Foundational metabolic findings were reported in 2015 (Lee et al., Cell Metabolism).

  3. 03

    All currently cited research is ; no controlled human clinical trials are cited on this profile.

Dossier overview

4

research areas

3

references

3

handling notes

01

Mechanism of action

Research literature has associated MOTS-c with AMPK pathway activation, nuclear translocation under metabolic stress (NRF2-related antioxidant gene regulation), and modulation of myostatin / muscle atrophy signalling in cell and mouse models.

02

Research applications

  • Mitochondrial-derived peptide biology
  • Metabolic homeostasis and insulin resistance research
  • Skeletal muscle atrophy research
  • AMPK and NRF2 pathway research

Evidence at a glance

What's behind this profile

3 citations · 2015–2021

Animal
3

Studies in rodents or other animal models.

Publication years

  1. 15
  2. 16
  3. 17
  4. 18
  5. 19
  6. 20
  7. 21
20152021

Counts are derived from the cited studies below. A study covering both in vivo and in vitro work is counted by its primary model. Sample size is reported in 0 of 3 citations. Findings remain model-specific and are not extrapolated to therapeutic use.

03

Study references

Each profile cites a minimum of two peer-reviewed sources, with model type and reported sample size where the source provides it. Findings are model-specific and must not be extrapolated to therapeutic use.

The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance

2015

Lee C et al. · Cell Metabolism

Model
In vivo and in vitro — mouse models of diet-induced obesity and skeletal muscle assays
Sample
Not reported in abstract

Reported that MOTS-c prevented diet-induced obesity and insulin resistance and activated AMPK in skeletal muscle in the mouse models used.

PMID 25738459 DOI 10.1016/j.cmet.2015.02.009

The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress

2018

Kim KH et al. · Cell Metabolism

Model
In vitro mechanistic cellular studies with in vivo mouse correlates
Sample
Not reported in abstract

Reported MOTS-c nuclear translocation under metabolic stress and AMPK-dependent regulation of antioxidant via NRF2 interaction.

PMID 29983246 DOI 10.1016/j.cmet.2018.06.008

MOTS-c reduces myostatin and muscle atrophy signaling

2021

Kumagai H et al. · American Journal of Physiology — Endocrinology and Metabolism

Model
In vitro skeletal muscle cell models and in vivo mouse correlates
Sample
Not reported in abstract

MOTS-c was associated with reduced myostatin expression and muscle atrophy signalling via the CK2-PTEN-mTORC2-AKT-FOXO1 pathway in the models used.

PMID 33554779 DOI 10.1152/ajpendo.00275.2020

Evidence caveats

  • All cited primary studies are preclinical (mouse and cell models). No PubMed-indexed controlled human clinical trials are cited on this profile.
  • MOTS-c is a relatively recently discovered peptide (2015); independent replication across research groups is still accumulating.

04

Storage and handling

Store under controlled laboratory conditions with batch and preparation details recorded.

  • Maintain batch and supplier documentation for short-peptide comparison work.
  • Protect material from contamination during handling.
  • Use protocol-specific storage documentation.