Buy MOTS-c Peptide Online — SourceTides ≥99% Purity Mitochondria-Derived Research Peptide 10mg Vial with CoA

Buy MOTS-c Peptide Online from SourceTides and receive a research-grade mitochondria-derived peptide (MDP) supplied at ≥99% purity, confirmed by reverse-phase HPLC and mass spectrometry on every production batch. MOTS-c — formally designated Mitochondrial Open Reading Frame of the 12S rRNA Type-c — is a 16-amino-acid peptide encoded within the mitochondrial genome, specifically within the MT-RNR1 gene (the 12S ribosomal RNA gene). It was discovered in 2015 by Changhan David Lee and colleagues at the USC Leonard Davis School of Gerontology and represents a landmark finding in mitochondrial biology: the first demonstration that the mitochondrial genome encodes bioactive peptides that function as systemic metabolic signals, not merely structural components of the mitochondrial ribosome.

MOTS-c carries the amino acid sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR) and has a molecular weight of approximately 2,174.64 g/mol. Circulating MOTS-c levels have been documented in blood and in mitochondria-containing tissues across species, and its natural plasma concentrations are significantly reduced in conditions including type 2 diabetes, obesity, gestational diabetes, and aging — positioning it as a research subject of high relevance in metabolic and longevity science. MOTS-c is often described as an exercise mimetic because it activates the same AMPK-driven metabolic cascade triggered by physical exercise, without the physical stimulus itself.

Every SourceTides MOTS-c 10 mg vial ships with a batch-specific Certificate of Analysis (CoA) and cold-chain packaging. This product is supplied exclusively for in-vitro and laboratory research purposes only and is not approved by the FDA, EMA, or any regulatory authority for human or veterinary therapeutic use.

MOTS-c Peptide 10 mg — Full Technical Specifications

What Is MOTS-c? Discovery, Mitochondrial Origins and Significance

MOTS-c is not a synthetic designer peptide — it is a naturally encoded signalling molecule whose existence was unknown until 2015. The landmark discovery came from Changhan David Lee, PhD, working in the Pinchas Cohen laboratory at the USC Davis School of Gerontology. Lee and colleagues identified a short open reading frame (sORF) within the 12S ribosomal RNA gene of human mitochondrial DNA — a region previously assumed to be entirely non-coding in the peptide sense — and demonstrated that this sORF is actively translated into a bioactive 16-amino-acid peptide. Their founding paper, published in Cell Metabolism in 2015, has accumulated over 820 citations and established MOTS-c as the cornerstone reference of the emerging mitochondria-derived peptide (MDP) field. (PubMed — Lee et al. 2015, Cell Metabolism, foundational MOTS-c paper)

What makes MOTS-c biologically unprecedented is its genomic origin. Unlike virtually all known peptide hormones and signalling molecules — which are encoded in the nuclear genome — MOTS-c is encoded by mitochondrial DNA and translated by the mitochondrial ribosome. This makes it one of a new class of molecules demonstrating that mitochondria, long conceptualised as passive energy factories, actively produce signalling molecules that communicate metabolic status systemically. Under stress conditions, MOTS-c translocates from the mitochondria to the nucleus, where it directly regulates gene expression at antioxidant response elements (AREs), acting as a transcriptional co-regulator. (PMC — Wan et al. 2023, J Translational Medicine, MOTS-c comprehensive review)

The amino acid sequence MRWQEMGYIFYPRKLR is highly conserved across mammalian species, suggesting evolutionary preservation of function. A genetic variant in the MOTS-c coding region (K14Q, the m.1382A>C polymorphism) has been documented to be significantly enriched in Japanese centenarians, providing a compelling genetic link between MOTS-c biology and exceptional human longevity. (MDPI Metabolites 2023 — MOTS-c functionally prevents metabolic disorders)

MOTS-c Mechanism of Action — Folate Cycle, AICAR and AMPK

MOTS-c operates through a precisely characterised molecular cascade that distinguishes it mechanistically from all other known metabolic peptides. Its primary pathway — the Folate–AICAR–AMPK axis — connects one-carbon metabolism, de novo purine biosynthesis, and the master energy-sensing kinase AMPK in a single regulatory chain.

Step 1 — Folate Cycle Inhibition

Under metabolic stress, MOTS-c disrupts the methionine-folate cycle inside cells. The folate cycle is the one-carbon metabolic network responsible for de novo purine biosynthesis, DNA methylation, and amino acid interconversion. By inhibiting folate-dependent purine synthesis, MOTS-c reduces consumption of 5-methyltetrahydrofolate (5-Me-THF) and diverts the metabolic flux of this pathway. (NIH Pharos — MOTS-c MT-RNR1 target profile)

Step 2 — AICAR Accumulation

Inhibition of de novo purine biosynthesis causes the intermediate 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to accumulate. AICAR is a well-characterised endogenous AMP analog and a potent activator of AMPK — the same mechanism exploited by the drug AICA riboside (acadesine) in pharmacological AMPK activation research. By generating AICAR endogenously through this folate cycle disruption, MOTS-c achieves AMPK activation through a physiologically integrated mechanism distinct from exogenous AMPK agonist approaches. (PubMed — Lee et al. 2015 Cell Metabolism; foundational pathway paper)

Step 3 — AMPK Activation and Downstream Metabolic Effects

Accumulated AICAR activates AMPK — often described as the master regulator of cellular energy balance. AMPK phosphorylation triggers a cascade of downstream metabolic effects including: upregulation of GLUT4 glucose transporter expression and membrane translocation in skeletal muscle cells (increasing glucose uptake); stimulation of fatty acid oxidation (beta-oxidation) in mitochondria; promotion of mitochondrial biogenesis via PGC-1α upregulation; and suppression of energy-consuming biosynthetic pathways. In combination, these effects produce a metabolic state closely resembling the cellular response to aerobic exercise — which is why MOTS-c has earned the designation “exercise mimetic” in the scientific literature. (PubMed — MOTS-c and exercise synergy via AMPK/PGC-1α, 2021)

Step 4 — Nuclear Translocation and Gene Regulation

Under conditions of metabolic stress, MOTS-c undergoes retrograde signalling from mitochondria to the nucleus — a process that has been experimentally verified and represents one of the most novel aspects of its biology. In the nucleus, MOTS-c binds to antioxidant response elements (AREs) in gene promoters and interacts with stress-response transcription factors including NRF2, ATF1, and ATF7, thereby directly regulating the expression of genes involved in antioxidant defence, metabolic adaptation, and cellular stress responses. This nuclear activity positions MOTS-c as both a metabolic hormone and a transcriptional co-regulator — a dual function unprecedented in mitochondrial peptide biology. (PMC — Wan et al. 2023, MOTS-c retrograde nuclear signalling)

Casein Kinase 2 (CK2) Binding

MOTS-c has been shown to bind to casein kinase 2 (CK2), a constitutively active serine/threonine kinase involved in cell survival, proliferation, and circadian rhythm regulation. The functional implications of this CK2 interaction are an active area of investigation and may provide an additional mechanistic layer beyond the primary AMPK pathway. (Wikipedia — MOTS-c identity and CK2 binding)

MOTS-c Peptide Research Areas — Evidence Summary Table

The following table maps the major research domains investigated in the MOTS-c preclinical and limited clinical literature, the experimental models studied, proposed mechanisms, and source references.

Human data referenced are observational/cross-sectional studies measuring circulating MOTS-c levels. Interventional human clinical trial data for exogenous MOTS-c is limited. All efficacy data is from preclinical (animal/in-vitro) models unless stated otherwise.

MOTS-c as an Exercise Mimetic — The Research Behind the Designation

The exercise mimetic designation for MOTS-c is mechanistically grounded, not merely a marketing analogy. Physical exercise activates AMPK in skeletal muscle through the increase in cellular AMP:ATP ratio that accompanies energy expenditure during activity. MOTS-c activates the same AMPK signalling cascade through an independent, non-exercise-dependent mechanism — the folate cycle inhibition and AICAR accumulation pathway described above — producing overlapping downstream metabolic effects in skeletal muscle cells.

A 2021 PubMed study directly examining the synergistic relationship between MOTS-c and exercise in C57BL/6 mice (high-fat diet model) demonstrated that the AMPK/PGC-1α axis mediates MOTS-c secretion in skeletal muscle, with treadmill training upregulating protein levels of MOTS-c, PGC-1α, and GLUT4 alongside phosphorylated AMPK and ACC. Critically, PGC-1α knockdown downregulated MOTS-c expression, while PGC-1α overexpression upregulated it — establishing a positive feedback relationship between exercise-induced metabolic signalling and MOTS-c expression. (PubMed — MOTS-c exercise synergy PGC-1α/AMPK 2021)

Research published in 2021 by Lee et al. (as cited in Cell Metabolism 2021) and detailed in the BioRxiv preprint demonstrated that MOTS-c treatment in middle-aged and old C57BL/6 mice (13.5 and 23.5 months) at 15 mg/kg/day three times weekly improved grip strength, gait analysis (stride length), 60-second walking test performance, treadmill running time and total distance, and blood glucose levels — all markers of physical capacity and metabolic health that decline with age. These findings position MOTS-c as a research tool for investigating age-related physical decline and the cellular mechanisms of exercise benefit in aged organisms.

MOTS-c, Aging, and Longevity Research — What the Data Shows

The association between MOTS-c and aging is multi-layered, encompassing both observational human data and interventional animal studies.

Observational data is clear: circulating MOTS-c levels decline with age. Research has documented that plasma MOTS-c concentrations can be up to 21% lower in older adults compared to younger counterparts. Furthermore, MOTS-c levels are significantly reduced in individuals with type 2 diabetes mellitus (particularly those with HbA1c >7%), gestational diabetes, obesity (including in children aged 5–14), and coronary endothelial dysfunction — all conditions characterised by impaired metabolic homeostasis that increase in prevalence with age. A systematic review and meta-analysis published in Diabetology & Metabolic Syndrome (2024) synthesised evidence from multiple databases, confirming the consistent pattern of reduced circulating MOTS-c in metabolic disease states. (PMC — MDP systematic review and meta-analysis 2024)

The longevity genetics data is particularly striking. A genetic variant in the MOTS-c coding sequence — the K14Q substitution caused by the m.1382A>C mitochondrial DNA polymorphism — is significantly enriched in Japanese centenarians (individuals living past 100 years). This genetic epidemiology finding suggests that variation in MOTS-c sequence or expression may contribute to exceptional longevity in humans, providing a biological rationale for the intense research interest in this peptide as a longevity science tool. (MDPI Metabolites 2023)

Circulating MOTS-c Levels in Human Health and Disease

The following table summarises key observations from human studies measuring circulating MOTS-c concentrations across different health conditions. This data informs the rationale for studying exogenous MOTS-c in preclinical models.

All data from observational human studies; no conclusions about causation or treatment efficacy for humans can be drawn from these measurements. Interventional human clinical trial data on exogenous MOTS-c is limited as of 2025.

High-Purity MOTS-c Peptide for Sale — SourceTides Quality Control

MOTS-c is a 16-amino-acid peptide with two methionine residues (positions 1 and 6) that are susceptible to oxidation if not handled and stored correctly during synthesis, lyophilisation, and transit. Oxidised methionine residues alter the peptide’s three-dimensional conformation and can interfere with AMPK-pathway activity in cell-based assays. SourceTides addresses this through strict synthesis handling protocols, nitrogen-atmosphere lyophilisation, and cold-chain packaging on all shipments.

MOTS-c Regulatory and Legal Status — 2025 Overview

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MOTS-c vs. Humanin — Mitochondria-Derived Peptide Comparison

MOTS-c and Humanin are both mitochondria-derived peptides (MDPs) encoded within the mitochondrial genome, but they differ fundamentally in sequence, mechanism, and research applications. Understanding this distinction is essential for protocol design.

Buy MOTS-c Peptide Online vs. Other Research Peptides — Comparison

MOTS-c Peer-Reviewed Research References

Frequently Researched Alongside MOTS-c — SourceTides Catalogue

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Frequently Asked Questions — Buy MOTS-c Peptide Online