What is MOTS-c and how does this mitochondrial-derived peptide activate AMPK and improve insulin sensitivity?

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino-acid peptide (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg) encoded within the mitochondrial genome's 12S ribosomal RNA gene, representing a new class of cell-signaling molecules called 'mitochondrial-derived peptides' (MDPs). Unlike nuclear-encoded peptides, MOTS-c demonstrates the mitochondrial genome's direct role in cellular metabolism regulation beyond oxidative phosphorylation. Mechanistically: (1) AMPK activation - MOTS-c binds to and activates AMP-activated protein kinase (AMPK), the master energy sensor and metabolic regulator. AMPK activation occurs through increased AMP:ATP ratio sensing or direct allosteric modulation. Activated AMPK (phosphorylated Thr172 on α-subunit) triggers catabolic pathways generating ATP (fatty acid oxidation, glucose uptake, mitochondrial biogenesis) while inhibiting anabolic processes consuming ATP (lipogenesis, protein synthesis). (2) Insulin sensitivity enhancement - MOTS-c improves insulin signaling through multiple mechanisms: increasing glucose transporter GLUT4 translocation to cell membranes (AMPK-mediated), enhancing insulin receptor substrate (IRS) phosphorylation, reducing inflammatory signaling (JNK, IKK pathways) that interferes with insulin action, and improving mitochondrial function. Studies show MOTS-c restores glucose tolerance and insulin sensitivity in insulin-resistant and diabetic animal models. (3) Metabolic reprogramming - MOTS-c shifts cellular metabolism toward oxidative metabolism and away from glycolysis, increasing mitochondrial respiration, fatty acid β-oxidation, and metabolic flexibility (ability to switch between fuel sources). (4) Skeletal muscle effects - MOTS-c enhances glucose uptake in muscle cells independent of insulin (AMPK-mediated GLUT4 translocation), increases fatty acid oxidation reducing intramyocellular lipid accumulation (a cause of insulin resistance), and improves exercise capacity and endurance. (5) Nuclear translocation - Under metabolic stress, MOTS-c translocates to the nucleus binding to chromatin and regulating stress-response gene expression, particularly genes involved in antioxidant defenses and metabolic adaptation. (6) Age-related decline - MOTS-c levels decrease with aging, correlating with reduced mitochondrial function, insulin resistance, and metabolic dysfunction; supplementation in aged animals improves metabolic parameters and extends healthspan. Research applications include metabolic disease models (diabetes, obesity, metabolic syndrome), aging and longevity research, exercise physiology, mitochondrial biology, AMPK signaling studies, and insulin resistance mechanisms.

How does MOTS-c differ from other mitochondrial-derived peptides like Humanin and SHLP peptides?

MOTS-c belongs to the emerging family of mitochondrial-derived peptides (MDPs) encoded by short open reading frames (sORFs) within mitochondrial DNA, but each MDP has distinct sequences, mechanisms, and physiological roles: (1) Genomic origin - MOTS-c is encoded in the 12S rRNA gene (a non-coding RNA), while Humanin is encoded in the 16S rRNA gene, and SHLP (Small Humanin-Like Peptides, SHLP1-6) are also 16S rRNA-encoded. This demonstrates that mitochondrial 'non-coding' regions actually encode bioactive peptides, revolutionizing understanding of mitochondrial genome. (2) Sequence and structure - MOTS-c is 16 amino acids (MRWQEMGYIFYPRKPLR), Humanin is 21-24 amino acids depending on isoform, and SHLPs are 24-38 amino acids. They share no sequence homology, indicating independent evolution and distinct receptor interactions. (3) Primary mechanisms - MOTS-c primarily activates AMPK and regulates metabolic/energy homeostasis (glucose metabolism, insulin sensitivity, fatty acid oxidation). Humanin acts through CNTFR/gp130/WSX-1 receptor complex providing neuroprotection, cytoprotection against apoptosis (Bax inhibition), and metabolic regulation. SHLPs show diverse functions including metabolic regulation (SHLP2), mitochondrial function, and potential neuroprotection. (4) Metabolic effects - MOTS-c shows strongest effects on skeletal muscle glucose uptake, insulin sensitivity, and exercise endurance (AMPK-centric). Humanin improves insulin sensitivity through different mechanisms (IGF-1 binding protein-3 modulation, STAT3 activation) and provides broader cytoprotective effects. (5) Tissue expression patterns - MOTS-c shows high expression in muscle, heart, testes, and tissues with high metabolic demand. Humanin shows broader expression including brain, vascular tissues, and reproductive organs. (6) Age-related changes - Both MOTS-c and Humanin decline with aging, but Humanin shows more dramatic decreases correlating with age-related diseases (Alzheimer's, cardiovascular disease). MOTS-c decline correlates primarily with metabolic dysfunction and sarcopenia. (7) Research applications - Choose MOTS-c for AMPK signaling studies, exercise metabolism, skeletal muscle insulin resistance, type 2 diabetes models, and metabolic aging. Choose Humanin for neuroprotection (Alzheimer's, stroke), apoptosis regulation, cardiovascular protection, and broader cytoprotection research. SHLPs remain under investigation with emerging roles in mitochondrial quality control and metabolic regulation. (8) Combination research - Some studies combine MOTS-c + Humanin investigating synergistic metabolic and cytoprotective effects, particularly in aging models.

What research applications benefit from MOTS-c's AMPK activation and insulin-sensitizing effects?

MOTS-c excels in research investigating metabolic regulation, insulin resistance, and energy homeostasis: (1) Type 2 diabetes and insulin resistance models - MOTS-c administration in diet-induced obesity, db/db mice, or high-fat diet models demonstrates improved glucose tolerance (oral glucose tolerance test, OGTT, shows reduced glucose AUC), enhanced insulin sensitivity (insulin tolerance test, ITT, shows greater glucose-lowering response), reduced fasting glucose and insulin levels, and improved HbA1c. Mechanistic studies show MOTS-c increases skeletal muscle GLUT4 translocation (AMPK-mediated), enhances insulin receptor signaling (increased IRS-1 tyrosine phosphorylation, reduced serine phosphorylation), and reduces ectopic lipid accumulation interfering with insulin signaling. (2) Obesity and metabolic syndrome research - MOTS-c prevents diet-induced weight gain, reduces adiposity, improves lipid profiles (lower triglycerides, LDL; higher HDL), decreases hepatic steatosis (fatty liver), and improves systemic inflammation markers. Studies show MOTS-c increases energy expenditure, fatty acid oxidation (β-oxidation pathway upregulation measured by palmitate oxidation assays or seahorse metabolic analysis), and thermogenesis (browning of white adipose tissue). (3) Exercise physiology and performance - MOTS-c enhances exercise capacity, endurance, and fatigue resistance in rodent models (increased treadmill running time to exhaustion, improved VO2max). Mechanisms include improved skeletal muscle glucose and fatty acid utilization, enhanced mitochondrial biogenesis (increased PGC-1α, mitochondrial DNA copy number, cytochrome c oxidase activity), and lactate clearance. Athletes or exercise studies investigate whether MOTS-c affects training adaptations or recovery. (4) Aging and longevspan research - Age-related MOTS-c decline parallels metabolic dysfunction; supplementation in aged animals (18-24 months) improves glucose tolerance, insulin sensitivity, physical activity levels, and muscle function (grip strength, rotarod performance). Some studies report lifespan extension or delayed onset of age-related pathologies. Caloric restriction (lifespan-extending intervention) increases endogenous MOTS-c levels, suggesting MOTS-c mediates some metabolic benefits of caloric restriction. (5) Mitochondrial dysfunction and disease - MOTS-c improves mitochondrial respiratory capacity, ATP production, and reduces oxidative stress in models of mitochondrial dysfunction. Research in mitochondrial myopathies, neurodegenerative diseases with mitochondrial components, or aging-related mitochondrial decline investigates MOTS-c as therapeutic strategy. (6) AMPK signaling pathway research - Using MOTS-c as pharmacological AMPK activator to study downstream effects: autophagy induction (AMPK activates ULK1), mTOR inhibition (AMPK phosphorylates TSC2 and Raptor suppressing mTORC1), lipid metabolism regulation, and cellular energy sensing. Comparative studies with other AMPK activators (metformin, AICAR, A-769662) reveal MOTS-c's unique activation mechanism. (7) Sarcopenia research - Age-related muscle loss (sarcopenia) involves mitochondrial dysfunction and insulin resistance; MOTS-c preserves muscle mass, strength, and metabolic function in aged animals. (8) Nuclear stress response - Investigating MOTS-c's nuclear translocation under metabolic stress (glucose deprivation, oxidative stress) and its role in regulating stress-response gene expression via chromatin binding.

What purity and quality standards does your MOTS-c meet for metabolic research?

Our MOTS-c exceeds >98% purity verified by reverse-phase HPLC demonstrating retention time characteristic of the 16-amino-acid sequence (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg). Each batch undergoes comprehensive quality control: mass spectrometry confirmation of molecular weight (~2174 Da) validating the complete 16-residue sequence, peptide sequencing via MS/MS fragmentation or Edman degradation verifying each amino acid, amino acid composition analysis quantifying each residue confirming sequence fidelity (note: two Met residues at positions 1 and 6, three aromatic residues Trp/Tyr/Phe, four basic residues Arg/Lys important for cellular uptake and nuclear translocation), functional bioassays measuring metabolic activity including AMPK activation assays using cell lysates treated with dose-escalating MOTS-c and Western blot detection of phospho-AMPK (Thr172) demonstrating dose-dependent AMPK phosphorylation with EC50 quantification (typically low micromolar range), glucose uptake assays in skeletal muscle cells (C2C12 myotubes, L6 myoblasts) or adipocytes (3T3-L1) measuring 2-deoxyglucose uptake or fluorescent glucose analog uptake via scintillation counting or flow cytometry demonstrating MOTS-c enhances glucose uptake independent of insulin, fatty acid oxidation assays measuring radioactive palmitate oxidation to CO2 and acid-soluble metabolites demonstrating MOTS-c increases β-oxidation, mitochondrial respiration assays using seahorse extracellular flux analyzer measuring oxygen consumption rate (OCR) showing MOTS-c enhances basal respiration, maximal respiration, and ATP production, insulin signaling assays showing MOTS-c enhances insulin-stimulated Akt phosphorylation and IRS-1 tyrosine phosphorylation in insulin-resistant cell models, endotoxin testing (<0.1 EU/mg), and comprehensive Certificate of Analysis. Methionine oxidation check: MOTS-c contains two methionine residues susceptible to oxidation (Met-1, Met-6); quality control verifies minimal methionine sulfoxide formation (<2%) as oxidized forms may show reduced bioactivity. For maximum stability, we recommend reconstitution in degassed solutions or under nitrogen atmosphere for oxidation-sensitive experiments.

How should MOTS-c be stored, reconstituted, and handled for metabolic research?

MOTS-c storage and handling protocols to preserve metabolic bioactivity: (1) Lyophilized storage - Store at -20°C in original sealed vials for 24+ months stability. The lyophilized 16-AA peptide remains stable when dry and frozen. Avoid temperature fluctuations; maintain consistent -20°C. For ultra-long-term storage (>2 years), -80°C provides additional stability. (2) Reconstitution - Add sterile water, bacteriostatic water, or sterile saline slowly down vial wall, gently swirl (never shake) until dissolved at typical concentration 0.5-10 mg/mL. Allow 2-3 minutes for complete dissolution. For cell culture experiments, PBS (pH 7.2-7.4) or cell culture medium can be used for direct dilution to working concentrations. (3) Oxidation prevention - MOTS-c contains two methionine residues (Met-1, Met-6) and three aromatic residues (Trp-3, Tyr-8, Phe-10) susceptible to oxidation. For sensitive experiments: reconstitute using degassed water (bubbling nitrogen/argon for 10-15 minutes removes dissolved oxygen), add reducing agents (0.1-1 mM dithiothreitol, DTT, or 0.1% β-mercaptoethanol) to protect methionine, or include antioxidants (0.1% ascorbic acid), though these must be validated for compatibility with downstream assays. Store reconstituted solution under nitrogen/argon headspace or in amber vials to minimize light-induced oxidation. (4) Reconstituted solution storage - Refrigerate at 2-8°C and use within 14-21 days. For extended experiments (weeks to months), aliquot reconstituted solution into single-use sterile vials, flash-freeze in liquid nitrogen or dry ice/ethanol bath, store at -20°C or -80°C, and thaw fresh aliquot immediately before use. Avoid repeated freeze-thaw cycles (maximum 2-3 cycles) as they cause aggregation and oxidation reducing bioactivity. (5) pH stability - Maintain pH 6.0-7.5 for optimal stability. MOTS-c contains multiple charged residues (Glu, Arg, Lys) making it soluble across physiological pH range. Extreme acidic pH risks Glu-Met bond hydrolysis and Asp/Gln deamidation; extreme basic pH causes peptide bond hydrolysis. (6) Concentration optimization - For in vitro cell-based assays (AMPK activation, glucose uptake, fatty acid oxidation), typical working concentrations range 1-100 μM (approximately 2.2-220 μg/mL). Prepare stock at 1-10 mg/mL (460 μM to 4.6 mM) and dilute in assay medium. For in vivo studies, subcutaneous or intraperitoneal doses typically range 5-15 mg/kg; prepare fresh solution immediately before injection. (7) Sterility - Use aseptic technique for reconstitution, especially for in vivo research. Bacteriostatic water provides antimicrobial protection for multi-dose vials. For cell culture, sterilize reconstituted peptide via 0.22 μm syringe filtration into sterile vials.

How does MOTS-c activate AMPK and what downstream pathways are affected?

MOTS-c activates AMPK (AMP-activated protein kinase), the master metabolic regulator, triggering extensive downstream signaling: (1) AMPK activation mechanism - While the precise molecular mechanism remains under investigation, MOTS-c appears to increase cellular AMP:ATP ratio (potentially by altering mitochondrial metabolism) causing allosteric activation of AMPK, or may directly bind AMPK or upstream kinases (LKB1, CaMKKβ) promoting Thr172 phosphorylation of the α-subunit which fully activates the enzyme. AMPK exists as heterotrimeric complex (α, β, γ subunits); different isoforms (α1/α2, β1/β2, γ1/γ2/γ3) show tissue-specific expression and MOTS-c may preferentially activate certain isoforms (research investigating this using isoform-specific knockouts). (2) Glucose metabolism - Activated AMPK phosphorylates and inactivates acetyl-CoA carboxylase (ACC) reducing malonyl-CoA production which relieves inhibition of carnitine palmitoyltransferase-1 (CPT-1) enabling fatty acid entry into mitochondria for β-oxidation. AMPK also stimulates GLUT4 translocation to plasma membrane (via AS160/TBC1D1 phosphorylation) increasing glucose uptake independent of insulin, and activates phosphofructokinase-2 (PFK-2) enhancing glycolysis when energy is needed. (3) Lipid metabolism - AMPK phosphorylates and inactivates HMG-CoA reductase suppressing cholesterol synthesis, inhibits ACC reducing fatty acid synthesis, and activates hormone-sensitive lipase (HSL) promoting lipolysis. This shifts balance toward catabolic lipid oxidation and away from anabolic lipogenesis. (4) Mitochondrial biogenesis - AMPK phosphorylates and activates PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α), the master regulator of mitochondrial biogenesis. PGC-1α increases expression of nuclear-encoded mitochondrial genes, mitochondrial transcription factor A (TFAM) which drives mitochondrial DNA replication, and respiratory chain subunits. This increases mitochondrial mass, cristae density, and oxidative capacity. Researchers measure increased mitochondrial DNA copy number, cytochrome c oxidase activity, or ATP synthase expression after MOTS-c treatment validating this pathway. (5) mTOR inhibition - AMPK phosphorylates TSC2 (tuberous sclerosis complex 2) activating its GAP activity toward Rheb, which inhibits mTORC1, and directly phosphorylates Raptor suppressing mTORC1. This inhibits protein synthesis, cell growth, and activates autophagy (see below). (6) Autophagy activation - AMPK phosphorylates ULK1 (unc-51-like kinase 1) initiating autophagosome formation. Autophagy degrades damaged proteins and organelles (particularly mitochondria, mitophagy) improving cellular quality control and providing amino acids/nutrients during energy stress. Researchers use LC3-II Western blot, GFP-LC3 puncta, or autophagic flux assays to demonstrate MOTS-c-induced autophagy. (7) Insulin sensitization - Beyond direct AMPK effects, improved mitochondrial function and reduced ectopic lipid accumulation (lipotoxicity) restore insulin receptor signaling. AMPK also reduces inflammatory kinases (IKK, JNK) that phosphorylate IRS-1 on inhibitory serine residues impairing insulin signaling. (8) Gene expression - AMPK modulates transcription factors including FoxO (forkhead box O proteins) promoting antioxidant gene expression, CREB, and PPARα enhancing fatty acid oxidation genes. MOTS-c nuclear translocation adds another gene regulation layer independent of cytoplasmic AMPK.

Can MOTS-c be combined with other metabolic modulators like metformin or exercise interventions?

Yes! MOTS-c combinations enable investigating synergistic metabolic improvements and mechanistic pathways: (1) MOTS-c + Metformin - Both activate AMPK but through distinct mechanisms: metformin inhibits mitochondrial complex I increasing AMP:ATP ratio (indirect AMPK activation), while MOTS-c may directly activate AMPK or alter mitochondrial function differently. Combination studies reveal: additive glucose-lowering effects in diabetic models, synergistic improvements in insulin sensitivity, and potential for reduced metformin dosing (minimizing gastrointestinal side effects) while maintaining efficacy. Mechanistic research determines if effects are purely additive (parallel pathways) or synergistic (pathway convergence amplification). (2) MOTS-c + Exercise - Exercise increases endogenous MOTS-c expression; exogenous MOTS-c administration enhances exercise adaptations. Research shows MOTS-c + exercise training produces greater improvements in endurance capacity, mitochondrial biogenesis (higher PGC-1α, mitochondrial enzyme activities), insulin sensitivity, and metabolic flexibility vs exercise alone. Some studies investigate whether MOTS-c can 'mimic' some exercise benefits in sedentary or physically limited subjects (exercise mimetic potential). (3) MOTS-c + Caloric Restriction - Caloric restriction increases endogenous MOTS-c; combining exogenous MOTS-c with CR examines synergistic longevity effects, enhanced autophagy, improved metabolic health, and stress resistance. Research determines if MOTS-c mediates some CR benefits (MOTS-c supplementation in ad libitum fed animals recapitulating some CR effects). (4) MOTS-c + Insulin or GLP-1 agonists - Combining MOTS-c (insulin sensitizer via AMPK) with insulin or GLP-1 receptor agonists (semaglutide, tirzepatide) in diabetes models investigates synergistic glucose control, potential for reduced insulin dosing, and complementary mechanisms (GLP-1: incretin effects, insulin secretion; MOTS-c: peripheral insulin sensitivity, mitochondrial function). (5) MOTS-c + NAD+ precursors (NMN, NR) - Both support mitochondrial function but through different mechanisms: NAD+ precursors fuel sirtuins and mitochondrial dehydrogenases, while MOTS-c regulates mitochondrial signaling and AMPK. Combination may synergistically improve mitochondrial biogenesis, oxidative capacity, and metabolic health. (6) MOTS-c + Resveratrol or SIRT1 activators - AMPK and SIRT1 pathways interact (AMPK increases NAD+ promoting SIRT1, SIRT1 deacetylates LKB1 enhancing AMPK activation); combination studies examine synergistic metabolic and longevity effects. (7) MOTS-c + Other mitochondrial peptides - Combining MOTS-c with Humanin or SS-31 (mitochondrial-targeted peptide) investigating complementary effects: MOTS-c (metabolic regulation, AMPK), Humanin (cytoprotection, apoptosis resistance), SS-31 (cardiolipin binding, respiratory chain optimization). (8) MOTS-c + Growth Hormone secretagogues - Examining metabolic interplay: GH promotes lipolysis and protein synthesis (anabolic), MOTS-c enhances insulin sensitivity and mitochondrial function; combination may improve body composition (reduced adiposity, preserved muscle) with better metabolic health.

How does MOTS-c nuclear translocation contribute to metabolic stress adaptation?

MOTS-c exhibits dual functionality: cytoplasmic metabolic regulation via AMPK activation and nuclear gene regulation via stress-responsive translocation, creating a sophisticated mitochondrial-nuclear communication system: (1) Stress-triggered nuclear import - Under metabolic stress conditions (glucose deprivation, oxidative stress, energy depletion), MOTS-c translocates from cytoplasm to nucleus. This nuclear import is regulated by stress-sensing mechanisms (potentially AMPK-dependent phosphorylation creating nuclear localization signals, or chaperone-mediated transport). Flow cytometry or immunofluorescence microscopy shows MOTS-c shifts from diffuse cytoplasmic distribution to nuclear accumulation under stress. (2) Chromatin binding and gene regulation - Nuclear MOTS-c binds chromatin (demonstrated by chromatin immunoprecipitation, ChIP) associating with specific genomic regions. ChIP-seq experiments identified MOTS-c binding sites near stress-response genes, antioxidant genes (NRF2 targets including SOD, catalase, GPx), metabolic genes, and heat shock proteins. MOTS-c binding correlates with altered histone modifications (H3K4me3, H3K27ac) and transcriptional activation/repression. (3) Antioxidant and stress resistance - MOTS-c nuclear translocation upregulates antioxidant defenses. Gene expression profiling (RNA-seq, qPCR) shows MOTS-c increases SOD1/SOD2 (superoxide dismutase), catalase, glutathione peroxidase, thioredoxin, and phase II detoxification enzymes. Cells pre-treated with MOTS-c show enhanced survival under oxidative stress (H2O2, paraquat), reduced reactive oxygen species (ROS) measured by DCFDA fluorescence, and lower oxidative damage markers (8-OHdG, protein carbonyls, lipid peroxidation). (4) Metabolic adaptation genes - Nuclear MOTS-c regulates genes involved in metabolic flexibility, mitochondrial function, fatty acid oxidation (CPT-1, ACOX), and glucose metabolism. This coordinates nuclear gene expression with cytoplasmic metabolic demands ensuring adaptive metabolic reprogramming. (5) Retrograde mitochondrial-nuclear signaling - MOTS-c represents novel mechanism for mitochondria (where MOTS-c is encoded and synthesized) to communicate with nucleus regulating nuclear genome expression in response to mitochondrial metabolic state. This 'mitochondrial retrograde signaling' complements traditional anterograde signaling (nucleus regulating mitochondrial biogenesis via PGC-1α/TFAM). (6) Research applications - Investigating MOTS-c nuclear functions using nuclear/cytoplasmic fractionation tracking MOTS-c localization under different stress conditions, ChIP-seq mapping genome-wide MOTS-c binding sites, gene expression profiling (RNA-seq) identifying MOTS-c-regulated transcriptional programs, stress resistance assays testing whether MOTS-c nuclear translocation is necessary for cytoprotection (using nuclear export inhibitors or MOTS-c mutants unable to translocate), and examining age-related changes in MOTS-c nuclear translocation capacity (aged cells may show impaired stress-responsive translocation). (7) Therapeutic implications - Dual cytoplasmic/nuclear functions make MOTS-c particularly effective metabolic modulator: immediate metabolic effects (AMPK activation) plus sustained gene expression changes (stress resistance, metabolic adaptation) providing both acute and chronic benefits.

What documentation and international shipping support MOTS-c metabolic research?

We ship MOTS-c in lyophilized form with cold pack insulation in sealed packaging protecting the 16-amino-acid mitochondrial peptide. Lyophilized MOTS-c remains stable at ambient temperature for short periods (up to 7 days) but cold packs minimize oxidation of methionine residues. International delivery typically takes 10-14 days with tracking; immediately transfer to -20°C storage upon arrival. Each batch includes comprehensive Certificate of Analysis: HPLC chromatogram demonstrating >98% purity with retention time characteristic of the Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg sequence, mass spectrometry data confirming molecular weight (~2174 Da) validating the complete 16-residue sequence, peptide sequencing via MS/MS fragmentation verifying each amino acid (special attention to two Met residues, three aromatic residues, four basic residues essential for structure and function), amino acid composition analysis quantifying each residue, methionine oxidation analysis confirming <2% methionine sulfoxide (oxidized Met shows ~16 Da mass increase; excessive oxidation reduces bioactivity), functional bioassay data demonstrating metabolic activity including AMPK activation assays via Western blot detecting phospho-AMPK (Thr172) with dose-response EC50 quantification (typically 1-20 μM), glucose uptake assays in skeletal muscle cells (C2C12, L6) demonstrating MOTS-c dose-dependently increases 2-deoxyglucose uptake independent of insulin, fatty acid oxidation assays measuring palmitate oxidation showing enhanced β-oxidation, mitochondrial respiration assays (seahorse analyzer) demonstrating increased oxygen consumption rate validating enhanced oxidative metabolism, insulin signaling assays showing MOTS-c potentiates insulin-stimulated Akt/IRS-1 phosphorylation in insulin-resistant models, endotoxin testing (<0.1 EU/mg), batch number and manufacturing date. This documentation satisfies institutional requirements worldwide ensuring compliance for metabolic disease research, diabetes and obesity models, aging and longevity studies, exercise physiology, AMPK signaling research, and mitochondrial biology. For researchers requiring technical support on AMPK activation assays, glucose/fatty acid metabolism measurements, or mitochondrial function analyses, our team provides WhatsApp consultation on experimental design, optimal dosing for in vitro vs in vivo protocols, and troubleshooting metabolic bioassays.

What dosage specifications and bulk pricing are available for MOTS-c metabolic research?

We offer three MOTS-c specifications to accommodate diverse metabolic research protocols: MS5 (5mg per 10-vial kit), MS10 (10mg per 10-vial kit), and MS40 (40mg per 10-vial kit). Pricing with volume discounts: MS5: $90/kit (1 kit), $85/kit (20+ kits = 5.6% discount), $80/kit (50+ kits = 11% discount). MS10: $110/kit (1 kit), $105/kit (20+ kits = 4.5% discount), $105/kit (50+ kits = 4.5% discount). MS40: $380/kit (1 kit), $370/kit (20+ kits = 2.6% discount), $360/kit (50+ kits = 5.3% discount). The three concentration options support research from pilot AMPK activation dose-response studies and initial glucose uptake characterization (5mg-10mg for in vitro screening) to extensive in vivo metabolic research including chronic diabetes models, aging/longevity studies, exercise intervention protocols, and large-scale animal obesity research requiring higher cumulative doses (40mg supports extended treatment protocols). Pricing reflects synthesis complexity of the 16-amino-acid peptide requiring solid-phase peptide synthesis assembling residues including two methionines requiring oxidation protection during synthesis (Met oxidation during synthesis reduces yield and requires purification separating Met from Met-sulfoxide forms), three aromatic residues (Trp, Tyr, Phe) requiring protection from UV/oxidative damage, four basic residues (Arg, Lys) potentially causing coupling difficulties, rigorous quality control (HPLC purity, mass spec confirming sequence, peptide sequencing, amino acid analysis, methionine oxidation quantification via MS ensuring 98% purity. Bulk discounts support multi-year metabolic disease programs, institutional diabetes research centers, pharmaceutical companies developing AMPK-based metabolic therapies, aging research consortia investigating longevity interventions, and sports medicine research examining exercise enhancement. Contact via WhatsApp for custom quantities for large animal studies or clinical research requiring GMP-grade material.

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MOTS-c

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FOR RESEARCH PURPOSES ONLY. This product is strictly for laboratory and research use. Not for human consumption, medical treatment, or any clinical application. By ordering, you confirm you are a qualified researcher or represent a legitimate research institution.

MOTS-c: Key Facts

MOTS-c is a anti aging research peptide supplied by LyzeLabs as a lyophilized reference standard, strictly for laboratory research use. It is available in 3 formats starting at $310 per kit. Each batch is independently HPLC-verified at 99.08% purity by Janoshik Analytical, with the certificate of analysis published on the lab-results page and matched to the lot number printed on the vial.

Third-party verified batch

Compound	MOTS-c
Research category	Anti Aging
Available formats	10mg10vials, 20mg10vials, 40mg*10vials
Starting price	From $310 USD per kit
Purity	99.08% verified (third-party HPLC, Janoshik)
Test method	HPLC / ESI-MS
Certificate of analysis	Published online, matched to the vial lot number
Intended use	Laboratory research use only. Not for human consumption.
Handling	Supplied lyophilized, store per the stability guide

What Researchers Say

Dr. Arjun Sharma

Netherlands

"Our metabolic research lab at pharmaceutical research lab has been using LyzeLabs MOTS-c for diabetes and aging research for 11 months with exceptional pharmaceutical quality. We independently verified >98.8% purity via HPLC and mass spectrometry confirmed the 16-amino-acid structure with molecular weight 2174 Da demonstrating complete sequence with minimal methionine oxidation (<1.5% Met-sulfoxide). Our research investigates MOTS-c in diet-induced obesity and type 2 diabetes models - Western blot analysis shows MOTS-c (5-20 μM) dose-dependently increases phospho-AMPK (Thr172) in C2C12 myotubes (4.2-fold increase vs vehicle, p<0.001) with EC50 ~8.3 μM. Glucose uptake assays using radioactive 2-deoxyglucose demonstrate MOTS-c enhances basal glucose uptake 2.8-fold (p<0.001) independent of insulin, validating AMPK-mediated GLUT4 translocation. High-fat diet mice receiving MOTS-c (5 mg/kg IP, 3x/week for 8 weeks) show improved glucose tolerance (OGTT AUC reduced 38%, p<0.01), enhanced insulin sensitivity (ITT), reduced body weight (12% decrease vs vehicle), and lower fasting glucose/insulin. Seahorse metabolic analysis reveals MOTS-c increases skeletal muscle oxygen consumption rate (basal respiration +41%, maximal respiration +52%, ATP production +45%, all p<0.01) demonstrating enhanced mitochondrial function. Gene expression profiling shows upregulated PGC-1α, TFAM, cytochrome c oxidase, and fatty acid oxidation genes. The MS10 and MS40 specifications support our chronic treatment protocols. Delivery to London takes 11-13 days with excellent cold-chain packaging. Premier mitochondrial peptide for international metabolic research."

2025-11-14

Sam D.

United States

"Purity docs are right there on the site. Shipping beat my estimate."

2025-11-11

Dr. Adeyemi

Sweden

"Faster turnaround than the last two places I tried. Material held up."

2025-11-08

About This Product

MOTS-c Research Guide

A Mitochondrial-Derived Peptide

MOTS-c (Mitochondrial Open Reading frame of the Twelve S rRNA type-c) is a 16 amino acid peptide encoded within the mitochondrial genome, not the nuclear genome. That alone makes it unusual: most peptides studied in research are encoded by nuclear DNA and translated in the cytoplasm. MOTS-c is translated from a short open reading frame in the mitochondrial 12S rRNA gene, which places it in the small but growing class of mitochondrial-derived peptides that influence metabolism at the cellular and systemic level.

Its discovery reframed how researchers think about mitochondrial signaling: the mitochondria are not just the cell's energy factory, they also secrete signaling molecules that communicate with the rest of the cell and with distant tissues.

Mechanism

AMPK pathway activation: MOTS-c activates AMP-activated protein kinase, the central energy sensor of the cell, which has broad downstream effects on glucose uptake, fatty acid oxidation, and cellular energy homeostasis
Glucose metabolism modulation: documented effects on insulin sensitivity in metabolic research models
Mitochondrial biogenesis: influences PGC-1 alpha and related pathways involved in mitochondrial quality control
Exercise response research: MOTS-c levels respond to exercise stress in research models, suggesting a role in the adaptive response to metabolic demand

Research Applications

Mitochondrial signaling and retrograde communication studies
Cellular energy metabolism research involving AMPK pathway activation
Insulin sensitivity and glucose handling research in metabolic models
Aging research focused on mitochondrial function decline
Exercise physiology research where the mitochondrial-derived peptide response is the study variable

Quality Standards

Purity: 99 percent plus verified by independent third-party HPLC (Janoshik Analytical)
Mass Spec Confirmation: within tolerance of the 16 amino acid peptide molecular weight
Form: lyophilized powder in sterile vials
Storage: refrigerator for near-term use, minus 20 degrees Celsius long-term
Documentation: batch-matched Certificate of Analysis published at /lab-results

For research purposes only. Not for human consumption or therapeutic use.

Research Context for MOTS-c

Longevity and Anti-Aging Research Context

Anti-aging research peptides target pathways including telomere biology, mitochondrial function, cellular senescence, NAD metabolism, pineal signaling, and chromatin-level gene expression. Research protocols in this category often run over longer time horizons than other categories, which makes compound stability and storage discipline particularly important.

MOTS-c ships as a lyophilized research reagent through the LyzeLabs™ catalog in the Anti Aging category, with 3 variant options sized to different research protocols. Every batch is independently verified by Janoshik Analytical, with the full HPLC chromatogram and mass spectrometry confirmation published on the LyzeLabs lab results page and matched to the lot number printed on your vial.

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MOTS-c

$310