MOTS-c Peptide (Research Use Only) MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a mitochondria-derived peptide (MDP) comprised of 16 amino acids. It has been detected in multiple tissues and in circulation, suggesting both local (cell-specific) and endocrine-like (“mitokine”) roles. Current preclinical literature links MOTS-c activity to AMP-activated protein kinase (AMPK) signaling and stress-responsive transcriptional programs. Mechanistic Context AMPK activation: Investigated in glucose uptake, lipid utilization, and cellular energy sensing. Mitonuclear signaling: Under metabolic stress MOTS-c has been reported to translocate to the nucleus and modulate ARE/NRF2-linked gene sets (stress response/antioxidant programs). Pathway targets: Literature explores effects on the folate–methionine cycle and de novo purine biosynthesis, with downstream AMPK engagement. Aging biology: Endogenous MOTS-c levels appear to change with age; interactions with NAD+/sirtuin networks are under study. Chemical Information Molecular Formula: C101H152N28O22S2 Molecular Weight: 2174.64 g/mol Synonyms: Mitochondria-derived peptide MOTS-c; ORF of 12S rRNA-c Sequence Length: 16 amino acids Highlights from Preclinical Studies Summaries below reflect cell and animal models; they do not imply outcomes in humans. Skeletal muscle & metabolism: In aged/insulin-resistant contexts, MOTS-c exposure has been associated with enhanced AMPK signaling, increased glucose transporter expression, and improved substrate handling in myoblasts and skeletal muscle models. Systemic energy balance: In diet-induced models, MOTS-c has been reported to influence the folate–methionine/purine axis, trigger AMPK, and support glucose utilization with leaner phenotypes and greater activity levels. Adipose & gene regulation: Nuclear translocation with modulation of antioxidant-response element genes (e.g., NRF2 programs) has been described, suggesting coordinated mito-nuclear crosstalk during stress. Bone biology: Osteogenic differentiation signals (↑ TGF-β1/β2, Smad7; ↑ osteogenic markers ALP, Runx2, Bglap) have been observed; effects attenuate when TGF-β1 is knocked down. Vascular/endothelial function: Associations between circulating MOTS-c and microvascular/epicardial endothelial reactivity have been reported; AMPK is a proposed mediator in endothelial models. Longevity signals: Age-related variation and sequence polymorphisms (e.g., Glu→Lys substitution) are being explored for functional impact on cellular lifespan pathways; mechanisms remain under investigation. Research Applications Energy-sensing/AMPK pathway interrogation Mitonuclear stress responses and NRF2 programs Skeletal muscle glucose handling and myogenesis Adipose and whole-body metabolic homeostasis Osteogenic differentiation/TGF-β–Smad signaling Endothelial biology and vascular reactivity models Product Details Size: 40 mg (custom sizes on request) Contents: MOTS-c, lyophilized Form: Lyophilized powder Purity: >99% (HPLC-verified) Storage: –20 °C (dry), protected from light/moisture Reconstitution: Sterile water or appropriate buffer; aliquot to avoid repeated freeze–thaw Stability (reconstituted): Short-term 2–8 °C; for extended storage, aliquot and freeze (investigator to confirm conditions)