MOTS-c is a mitochondrial-derived peptide: a short peptide encoded not in nuclear DNA but within the
mitochondrial genome, in a small open reading frame inside the 12S ribosomal RNA region. It was described by Lee and
colleagues in 2015 and is studied as an example of mitochondrial-to-nuclear signalling.
Product page: MOTS-c.
Identity
PubChem catalogues MOTS-c under CID 146675088 with the molecular formula
C101H152N28O22S2 and a molecular weight of approximately
2174.6 g/mol. It is a 16-amino-acid peptide. The name is an abbreviation of “mitochondrial open reading
frame of the 12S rRNA type-c”, which describes where its coding sequence sits rather than what it does.
What “mitochondrial-derived peptide” means
The mitochondrial genome is small and was long assumed to encode only components of the respiratory chain plus the
RNAs needed to translate them. Mitochondrial-derived peptides are short sequences found within that genome, outside
those canonical genes, that appear to be translated and to act outside the mitochondrion. MOTS-c is one of the
best-characterised examples; humanin is another.
This classification is why MOTS-c is discussed alongside bioenergetic research materials rather than with receptor
agonists: the research interest is in retrograde signalling from mitochondria to the nucleus.
Research context
The originating paper by Lee and colleagues examined skeletal-muscle and whole-body metabolic signalling endpoints in mouse models and described
an AMPK-linked mechanism involving inhibition of the folate cycle and de novo purine biosynthesis, placing MOTS-c within research on cellular energy sensing. Subsequent literature has extended
into a range of tissue, cell-type and stress-response models, including work on the peptide’s nuclear translocation under metabolic stress. Readers should note the study designs: this is animal and cell-culture work,
and the endpoints measured in those papers are not statements about humans.
Where laboratory work concerns mitochondrial and bioenergetic pathways more broadly,
NAD+ is the other material in this catalog studied in that context. The two are not
interchangeable and are not the same kind of molecule: NAD+ is a coenzyme, not a peptide, and the overlap is the
research area rather than the chemistry.
Limitations of the current evidence
- The field is young; MOTS-c was first described in 2015.
- Most published endpoints are in rodent models or cultured cells.
- Detection and quantification methods for endogenous mitochondrial-derived peptides are still being standardised,
which affects how circulating-level findings should be read. - No regulatory approval exists for any mitochondrial-derived peptide.
Research use only
Supplied strictly for in-vitro laboratory research. This page describes identity, classification and research
context. It contains no dosing, administration, performance or treatment information.
References
Lee C. et al. (2015). Cell Metab, 21(3):443–54. PMID 25738459.
PubChem. MOTS-c — Compound Summary, CID 146675088. National Library of Medicine.