What is MOTS-c? A research overview of the 16-amino-acid mitochondrial-derived peptide: origin, sequence, AMPK signaling studies, and lab handling notes.
For research use only. Not for human or veterinary use.
Quick answer: MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded by a short open reading frame inside the mitochondrial 12S rRNA gene (MT-RNR1). It was first described by Lee and colleagues in 2015 and is studied as a mitochondrial-derived peptide (MDP) involved in cellular metabolic signaling, particularly the AMPK pathway. Research on MOTS-c is preclinical: cell-culture and animal-model studies.
Key facts at a glance
- Name: MOTS-c (mitochondrial ORF of the 12S rRNA type-c)
- Class: Mitochondrial-derived peptide (MDP)
- Length: 16 amino acids
- Sequence: MRWQEMGYIFYPRKLR
- Approx. molecular weight: ~2,174.6 Da (average mass, free acid)
- Gene origin: Short ORF within mitochondrial MT-RNR1 (12S rRNA)
- First described: Lee et al., Cell Metabolism, 2015
- Typical supply form: Lyophilized powder
Molecular weight is calculated from the sequence. Always use the value reported on the batch COA for your material.
Where MOTS-c comes from
Most of the proteins in a cell are encoded by nuclear DNA. Mitochondria carry their own small genome, which was long thought to encode only 13 proteins plus the rRNAs and tRNAs they need. Researchers later found that short open reading frames inside mitochondrial genes can encode small bioactive peptides. These are called mitochondrial-derived peptides. The first identified was humanin (encoded in the 16S rRNA region). MOTS-c, encoded in the 12S rRNA region, was reported in 2015.
This makes MOTS-c interesting to researchers for a basic reason: it's a possible route for mitochondria to send signals to the rest of the cell, the opposite direction to most well-studied nuclear-to-mitochondrial signaling.
What MOTS-c research has examined
AMPK signaling and the folate cycle
In the original 2015 work, Lee et al. reported that MOTS-c acts on the folate cycle and de novo purine biosynthesis in cultured cells. This led to accumulation of the intermediate AICAR, which is a known activator of AMP-activated protein kinase (AMPK), a central regulator of cellular energy status. Much MOTS-c research since then uses it as a tool for studying AMPK-linked metabolic signaling in vitro and in rodent models.
Nuclear translocation under metabolic stress
In 2018, Kim et al. reported that MOTS-c can move from the cytoplasm into the nucleus of cells under metabolic stress (for example, glucose restriction or oxidative stress) and that it was associated with changes in the expression of nuclear genes, including antioxidant-response-element (ARE) genes linked to NRF2. This work positioned MOTS-c as a candidate mitonuclear communication signal.
Ongoing research directions
Published preclinical work also examines MOTS-c in relation to cellular stress responses, skeletal-muscle cell metabolism and aging-related biology in model systems. These are areas of active investigation; findings in cell and animal models don't establish effects in humans.
Working with MOTS-c in the lab
- Identity and purity: confirm identity by mass spectrometry (the observed mass should match the expected mass for the sequence) and purity by reversed-phase HPLC. See HPLC vs. Mass Spectrometry.
- Content vs. purity: HPLC purity isn't the same as the amount of peptide in the vial. Lyophilized peptides also contain counter-ions and water. See Net Peptide Content vs. HPLC Purity.
- Sequence features: MOTS-c contains two methionine residues and a tryptophan, which are prone to oxidation. Minimize air and light exposure and avoid repeated freeze-thaw cycles once it's in solution.
- Storage: store the lyophilized powder cold, dry and protected from light, and record the batch number with every experiment. See Lyophilized Peptide Storage and Handling.
- Documentation: match the lot on your vial to its COA and verify the COA with the issuing lab.
Related research reagents
MOTS-c is often discussed alongside cellular energy metabolism and redox cofactors. For background on the coenzyme at the center of many of those pathways, see our NAD+ research overview.
QC Labs MOTS-c
QC Labs supplies MOTS-c (10 mg, lyophilized) for in vitro and laboratory research. COAs are available for each listed batch in the COA Library.
References
- Lee C, Zeng J, Drew BG, et al. Cell Metabolism. 2015;21(3):443–454. doi:10.1016/j.cmet.2015.02.009
- Kim KH, Son JM, Benayoun BA, Lee C. Cell Metabolism. 2018;28(3):516–524.e7. doi:10.1016/j.cmet.2018.06.008
- Hashimoto Y, Niikura T, Tajima H, et al. PNAS. 2001;98(11):6336–6341. doi:10.1073/pnas.101133498 (discovery of humanin, the first mitochondrial-derived peptide)
Frequently asked questions
What does MOTS-c stand for? Mitochondrial open reading frame of the 12S rRNA type-c.
How many amino acids are in MOTS-c? Sixteen: MRWQEMGYIFYPRKLR.
Is MOTS-c a mitochondrial protein? It's encoded in the mitochondrial genome, but research indicates it acts outside mitochondria as a signaling peptide, including in the cytoplasm and, under stress, in the nucleus.
What pathway is MOTS-c most studied in? AMPK-linked metabolic signaling, following the folate-cycle and AICAR findings reported in 2015.
For research use only. Not for human or veterinary use. QC Labs products are laboratory reagents and are not intended to diagnose, treat, cure, or prevent any disease. Nothing in this article describes or suggests human use. See our Research Disclaimer.
For Research Use Only • Not for Human Consumption
This article is provided for educational purposes. QC Labs products are intended for laboratory research only.
