#Genetic | #Longevity | #Metabolic | #Mitochondrial

MOTS-c — Mitochondrial-Derived Peptide (MDP)

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid peptide encoded within mitochondrial DNA. It belongs to the class of mitochondrial-derived peptides (MDPs) and serves as a critical mechanistic research tool for investigating mitochondrial–nuclear communication, metabolic stress–responsive signaling, and cellular energy homeostasis. This compound is supplied exclusively for in-vitro laboratory research use.

Peptide Name

MOTS-c

Sequence Length

16 amino acids

Amino Acid Sequence

Met–Arg–Trp–Gln–Glu–Met–Gly–Tyr–Ile–Phe–Tyr–Pro–Arg–Lys–Leu–Arg

Molecular Formula

C₁₀₁H₁₅₂N₂₈O₂₂S₂

Molecular Weight

2174.64 g/mol

Synonyms

Mitochondrial Open Reading Frame of the 12S rRNA-c

Form

Lyophilized Powder

Origin

Encoded by the 12S rRNA region of the mitochondrial genome, challenging the traditional view that mitochondrial DNA encodes only 13 proteins.

Translocation

Exhibits the ability to translocate from mitochondria to the nucleus under metabolic stress conditions to regulate gene expression.

Stability

Highly susceptible to enzymatic degradation in serum; requires careful handling in cell culture systems.

Store powder at +4°C (short term) or -20°C (long term). Keep desiccated.

For laboratory research use only. Reconstitute using sterile water, bacteriostatic water, or an appropriate sterile buffered solution consistent with laboratory research protocols. Preparation should be performed under aseptic conditions. Reconstituted material is not intended for long-term storage.

Stability

MITOCHONDRIAL–NUCLEAR SIGNALING & GENE REGULATION

MOTS-c is a primary subject in studies investigating retrograde signaling pathways between mitochondria and the nucleus.

Nuclear Translocation: Under metabolic stress, MOTS-c translocates to the nucleus and interacts with transcriptional regulators (e.g., NRF2, antioxidant response elements) to modulate adaptive gene expression.
Transcriptional Control: Research examines its role in regulating genes associated with antioxidant defense and glucose metabolism homeostasis.

METABOLIC STRESS–ASSOCIATED SIGNALING PATHWAYS

A central focus of MOTS-c research is its involvement in cellular energy-sensing pathways.

Folate Cycle Inhibition: Research indicates MOTS-c restricts de novo purine synthesis via folate-methionine cycle modulation, resulting in accumulation of AICAR.
AMPK Activation: Increased intracellular AICAR levels are used to study activation of AMP-activated protein kinase (AMPK), a master regulator of cellular energy balance.

SKELETAL MUSCLE & CELLULAR ENERGY ADAPTATION MODELS

In muscle-derived cell models, MOTS-c is used to assess metabolic adaptation.

Glucose Uptake: Assays compare insulin-stimulated versus MOTS-c-stimulated GLUT4 translocation in myotube cultures.
Beta-Oxidation: Studies investigate effects on fatty acid oxidation rates and mitochondrial respiration capacity (oxygen consumption rate, OCR).

STRESS-RESPONSIVE & AGING-CONTEXT RESEARCH

Given age-associated mitochondrial decline, MOTS-c is a probe for adaptive stress signaling research.

Mitohormesis: Research examines how low-level mitochondrial stress signals mediated by MOTS-c trigger cytoprotective adaptations.
Senescence Markers: Studies evaluate correlations between endogenous MOTS-c levels and biomarkers of cellular aging across tissues.

RESEARCH CONTEXT & LIMITATIONS

Short Half-Life: Rapid degradation by serum proteases often necessitates protease inhibitors or frequent replenishment in extended assays.
Species Specificity: Subtle sequence variations between species may affect cross-reactivity in non-human research models.
Delivery Mechanisms: Intracellular delivery can be challenging in certain cell lines and may require permeabilization agents or transfection strategies.

KEY SCIENTIFIC REFERENCES

Lee, C., et al. (2015).
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.
Cell Metabolism.
Kim, K. H., et al. (2018).
MOTS-c regulates insulin sensitivity and metabolic homeostasis via AMPK activation.
Cell Reports.
Lee, C., et al. (2016).
Mitochondrial-derived peptides: Are we underestimating the power of the mitochondrial genome?
Trends in Endocrinology & Metabolism.
Reynolds, J. C., et al. (2021).
Mitochondrial-derived peptides: Emerging regulators of metabolism and longevity.
American Journal of Physiology – Endocrinology and Metabolism.

The compound listed below is referenced in research contexts related to the mechanisms discussed in this article.

MOTS-c is a chemical reagent and peptide reference standard intended strictly for in-vitro and laboratory research applications (e.g., cell signaling assays, gene expression analysis). It is not a drug, dietary supplement, or performance enhancer. It is not intended for human consumption or therapeutic use. All handling must be performed by qualified professionals in a laboratory setting.

MOTS-c — Mitochondrial-Derived Peptide (MDP)

Peptide Name

Sequence Length

Amino Acid Sequence

Molecular Formula

Molecular Weight

Synonyms

Form

Origin

Translocation

Stability

Stability

Age Verification Required

GLP2-T

Thymosin Alpha-1 (TA1)

Tesamorelin

TB-500

SS-31

Semax

Selank

GLP3-R

PT-141