What Is MOTS-c?
MOTS-c is a 16-amino-acid mitochondrial-derived peptide that has become an important research model for studying communication between mitochondria and the rest of the cell.
Unlike most familiar cellular peptides, MOTS-c is associated with genetic information located within the mitochondrial genome rather than a conventional nuclear protein-coding gene.
The peptide was reported in 2015 after researchers identified a short open reading frame within the mitochondrial 12S ribosomal RNA region. The resulting peptide was named MOTS-c, short for mitochondrial open reading frame of the 12S rRNA-c.
Since that discovery, MOTS-c research has expanded into mitochondrial signaling, cellular stress responses, AMPK-associated pathways, nuclear translocation and the broader field of communication between mitochondrial and nuclear systems.
MOTS-c at a Glance
| Characteristic | Information |
|---|---|
| Name | MOTS-c |
| Full Name | Mitochondrial Open Reading Frame of the 12S rRNA-c |
| Compound Type | Mitochondrial-derived peptide |
| Sequence Length | 16 amino acids |
| Amino-Acid Sequence | MRWQEMGYIFYPRKLR |
| CAS Number | 1627580-64-6 |
| PubChem CID | 146675088 |
| Molecular Formula | C101H152N28O22S2 |
| Molecular Weight | Approximately 2174.6 g/mol |
| Research Focus | Mitochondrial signaling and mitonuclear communication |
PubChem lists MOTS-c as a 16-residue peptide with the sequence MRWQEMGYIFYPRKLR, molecular formula C101H152N28O22S2 and calculated molecular weight of approximately 2174.6 g/mol.
What Does MOTS-c Stand For?
The name MOTS-c originates from:
Mitochondrial Open Reading Frame of the 12S rRNA-c
The unusual name reflects the peptide’s genetic origin.
The original discovery study identified a 51-base-pair short open reading frame, or sORF, associated with mitochondrial 12S rRNA. The work helped expand the concept that mitochondrial DNA may encode signaling molecules in addition to the better-known mitochondrial components involved in cellular bioenergetics.
What Is a Mitochondrial-Derived Peptide?
Mitochondrial-derived peptides, often abbreviated MDPs, are small peptides associated with short open reading frames in mitochondrial genetic regions.
They have become scientifically interesting because mitochondria are now understood as more than cellular energy-producing organelles.
Mitochondria also participate in:
- cellular stress signaling
- redox regulation
- metabolite sensing
- communication with the nucleus
- signaling between intracellular compartments
MOTS-c is particularly important in this field because subsequent studies showed that it may participate in signaling extending from mitochondrial systems toward the nucleus.
Where Is MOTS-c Encoded?
MOTS-c is associated with the mitochondrial 12S rRNA region, also referred to as MT-RNR1.
This distinguishes it from the overwhelming majority of human proteins and peptides, which originate from nuclear DNA.
The discovery of MOTS-c contributed to a growing view that mitochondrial genetic information may contain previously underappreciated short open reading frames capable of producing biologically active peptides.
What Is the MOTS-c Sequence?
The recognized 16-amino-acid sequence is:
MRWQEMGYIFYPRKLR
Written by residue:
Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
PubChem reports the same sequence and an approximate molecular weight of 2174.6 g/mol.
Sequence identity is particularly important when evaluating synthetic peptide research materials because a product name alone does not fully characterize the molecular material.
Analytical documentation should correspond to the actual material and production lot being evaluated.
MOTS-c and Mitonuclear Communication
One of the most important developments in MOTS-c research occurred when investigators reported that the peptide could move toward the nucleus under metabolic-stress conditions.
A 2018 study in Cell Metabolism found that MOTS-c could translocate to the nucleus following metabolic stress and participate in regulation of nuclear gene expression through an AMPK-associated mechanism. The researchers also reported interactions with stress-responsive transcriptional systems.
This finding was important because it presented an experimental model of signaling moving in the opposite direction from the more familiar nucleus-to-mitochondria pathway.
Instead:
mitochondrial-associated genetic information → peptide → nuclear signaling
This broader concept is commonly described as mitonuclear communication.
MOTS-c and AMPK-Related Research
AMP-activated protein kinase, or AMPK, is widely studied as a cellular signaling system involved in sensing changes in cellular energetic conditions.
The original 2015 MOTS-c paper connected MOTS-c-associated metabolic signaling with changes involving the folate cycle, de novo purine synthesis and AMPK activation in experimental systems.
The later 2018 nuclear-translocation research also described MOTS-c regulation of nuclear gene expression as AMPK-dependent under the experimental conditions studied.
These findings make AMPK one of the recurring mechanistic themes in MOTS-c research.
Why Is Nuclear Translocation Important?
Cellular location can be highly relevant to biological signaling.
A molecule present primarily in the cytoplasm may participate in very different processes from one interacting with nuclear transcriptional systems.
The 2018 MOTS-c study reported changes in MOTS-c cellular localization under metabolic stress and described regulation of a broad range of genes associated with stress responses.
More recent research has attempted to identify the molecular machinery involved in that translocation.
A 2025 Redox Biology study reported experimental evidence involving MYH9-dependent nuclear transport of MOTS-c in a lung ischemia-reperfusion model.
That work provided a more specific mechanistic framework for studying how MOTS-c might physically participate in mitochondria-to-nucleus signaling.
What Research Areas Involve MOTS-c?
MOTS-c now appears in research involving several interconnected areas:
Mitochondrial signaling
Researchers study MOTS-c as one example of information potentially originating from mitochondrial genetic systems and affecting other cellular compartments.
Cellular stress
MOTS-c localization and signaling have been studied under experimentally induced metabolic and oxidative stress.
Nuclear gene regulation
Studies have investigated MOTS-c interaction with transcriptional systems and stress-responsive gene expression.
AMPK-associated pathways
AMPK-related signaling appears repeatedly in foundational MOTS-c literature.
Mitochondrial-derived peptides
MOTS-c is frequently studied alongside the broader emerging class of mitochondrial-derived signaling peptides.
What Does Current Research Not Establish?
It is important to distinguish experimental findings from conclusions that extend beyond the studied model.
Much of the MOTS-c literature remains:
- mechanistic
- cellular
- animal-based
- preclinical
- model-specific
Findings from cultured cells, rodents or experimentally induced disease models should not automatically be interpreted as establishing effects in humans.
Similarly, published biological research does not establish the identity or purity of a commercial research-material lot.
Those are separate questions requiring analytical documentation.
MOTS-c Research and Analytical Identity
Researchers evaluating MOTS-c material should distinguish:
Scientific identity:
What molecule is MOTS-c?
from:
Analytical identity:
Does a particular research-material lot correspond to the expected molecule?
and:
Purity:
What does a validated chromatographic method indicate about sample composition?
These questions require different evidence.
A literature reference cannot substitute for lot-specific analytical testing.
Selected Scientific References
PubChem Compound 146675088 — MOTS-c.
Related MOTS-c Research Resources
- MOTS-c 10 mg Research Peptide
- MOTS-c Sequence, Structure and Molecular Characteristics
- MOTS-c Research in 2026
- MOTS-c Analytical Testing
FOR LABORATORY RESEARCH ONLY. NOT FOR HUMAN OR VETERINARY USE OR CONSUMPTION.
Continue the MOTS-c Research Cluster
View MOTS-c 10 mg Research Peptide for the product-specific research-material page.
