Research Spotlight

MOTS-c: Research Overview

PūrTONIX Analytical TeamMarch 18, 20253 min read

Research Use Only — Regulatory Notice

All information contained in this article is derived exclusively from publicly available scientific literature, peer-reviewed academic publications, and publicly accessible research databases. This content is provided strictly for educational and informational purposes in the context of laboratory research.

PūrTONIX does not make any medical, therapeutic, or clinical claims. None of the compounds discussed have been approved by the U.S. Food and Drug Administration (FDA) for human use, diagnosis, treatment, or prevention of any disease or condition, except where explicitly noted for approved pharmaceutical forms.

This article does not constitute medical advice. These compounds are sold by PūrTONIX strictly as laboratory research reagents for in vitro use only. They are not intended for human or veterinary administration, dietary supplementation, or any therapeutic application.

All citations reference publicly available research. PūrTONIX makes no representations regarding the replication, accuracy, or applicability of any referenced study.

Compound Overview

Full name: Mitochondrial Open Reading Frame of the 12S rRNA-c peptide (L-methionyl-L-arginyl-L-tryptophanyl-L-glutaminyl-L-glutamyl-L-methionyl-L-glycyl-L-tyrosyl-L-isoleucyl-L-phenylalanyl-L-tyrosyl-L-prolyl-L-arginyl-L-lysyl-L-leucyl-L-arginine)
Molecular formula: C100H152N28O22S2
Molecular weight: 2173.55 g/mol
Sequence / class: 16-residue mitochondrial-derived peptide encoded within the 12S rRNA locus of the mitochondrial genome (MRWQEMGYIFYPRKLR)
Receptor targets: Published in vitro literature describes engagement with AMP-activated protein kinase (AMPK) signaling cascades and reported folate-cycle interactions in cellular models
Research classification: Mitochondrial-derived peptide (MDP) research reagent for in vitro mitochondrial signaling and AMPK pathway studies
PubChem CID: 118644362

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-residue peptide encoded within the 12S ribosomal RNA locus of the mitochondrial genome. The sequence MRWQEMGYIFYPRKLR translates from a short open reading frame embedded in the mitochondrial DNA and was the founding member of the mitochondrial-derived peptide (MDP) family described in publicly available research. The molecular formula is C100H152N28O22S2 with two methionine residues that require attention during analytical handling.

Published literature classifies MOTS-c as a mitochondrial-derived peptide research reagent. The compound has emerged as a tractable analytical probe for in vitro studies of mitochondrial-nuclear signaling and AMP-activated protein kinase (AMPK) pathway engagement. The 16-residue size makes it accessible to standard solid-phase synthesis at analytical scale, and the lyophilized peptide is stable enough for routine in vitro assay use under conventional storage conditions.

Research published in the peer-reviewed literature has used MOTS-c to study mitochondrial biochemistry from an endocrine perspective, reframing mitochondria as organelles that actively encode regulatory signals rather than functioning only as bioenergetic compartments. The peptide sits alongside humanin and the SHLP family within the broader MDP literature, and comparative in vitro panels across these peptides have provided mechanistic context for the family as a whole.

Published research suggests that MOTS-c translocates into the nucleus under metabolic-stress conditions in cellular models, providing a direct mechanistic link between cytoplasmic mitochondrial signaling and nuclear gene expression. This translocation behavior has been characterized in cellular fractionation experiments and in fluorescence-microscopy studies described in publicly available literature.

Molecular Structure

MOTS-c

C100H152N28O22S2

Molecular weight 2173.55 g/mol

Structure reference: Public domain chemical databases (PubChem CID 118644362).

In Vitro Research Applications

The following applications reflect published in vitro and preclinical research only. None of these applications constitute approved medical use.

Published in vitro applications of MOTS-c include its use in AMPK phosphorylation assays, glucose-uptake biochemistry assays in skeletal muscle cell lines, and cellular fractionation experiments that read out nuclear translocation kinetics. Investigators have used the peptide to characterize how mitochondrial-encoded signals propagate to nuclear-encoded gene expression programs under controlled in vitro conditions.

Receptor-binding studies indicate that MOTS-c does not engage a single classical G-protein-coupled receptor; instead, the published literature describes pathway-level effects on AMPK activation, downstream metabolic flux readouts, and transcriptional readouts of nuclear-encoded mitochondrial genes in cellular models.

Comparative panels with humanin and the SHLP family allow investigators to isolate MDP-specific pharmacology from background mitochondrial signaling, with identical lot-release standards across the panel as a prerequisite for the comparison to mean anything analytically.

Published Research Highlights

[1]A study published in Cell Metabolism (2015) examined the mitochondrial-derived peptide MOTS-c in cellular models with AMPK pathway and metabolic-flux readouts.
[2]A study published in Trends in Endocrinology and Metabolism (2018) reviewed publicly available literature on mitochondrial-derived peptides and their in vitro signaling biochemistry.
[3]A study published in Aging Cell (2018) investigated MOTS-c translocation biochemistry in cellular models under defined metabolic-stress conditions.

The above represents a non-exhaustive summary of publicly available research. PūrTONIX does not endorse, validate, or make claims based on any referenced study.

Analytical Considerations for Laboratory Use

Published chemical property data indicate that MOTS-c is soluble in water and in standard aqueous assay buffers. The lyophilized peptide is stored at -20°C under inert atmosphere with attention to the two methionine residues, which are susceptible to oxidation under uncontrolled storage. Reconstituted stocks are held in single-use aliquots to preserve analytical reproducibility in sensitive AMPK reporter assays.

Reconstitution in bacteriostatic water or in assay-matched buffer is standard for in vitro AMPK and mitochondrial signaling assays. Analytical characterization commonly includes reverse-phase HPLC purity analysis, electrospray mass spectrometry confirming the 16-residue sequence with intact methionine signals, and residual solvent screening per ICH Q3C.

Handling recommendations are based on published chemical property data and are intended for qualified laboratory personnel only.

Research-Grade Sourcing Standards

AMPK reporter assays in cellular models are sensitive to deletion peptides and to methionine oxidation byproducts. Material characterized for high chromatographic purity with documented mass-spectral identity provide the analytical baseline for reproducible MDP research.

View MOTS-c in the Research Catalog →Browse Product Documentation →