MOTS-c — Mitochondria-Derived Peptide (16 aa)

MOTS-c is a short peptide encoded in the mitochondrial genome (within the 12S rRNA region). In research, it’s used to explore cellular energy sensing, stress adaptation, and insulin sensitivity with a focus on AMPK-linked pathways.

Identifiers

CAS: 1627580-64-6
PubChem CID: 146675088
Formula / MW: C₁₀₁H₁₅₂N₂₈O₂₂S₂ · ≈ 2174.6 Da
Sequence (human): Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR)
Origin: Encoded by mitochondrial DNA (not nuclear DNA)

How It Works (Plain English)

MOTS-c helps cells sense low-energy states and activates AMPK, a master regulator of energy balance.
It’s linked to the folate–AICAR–AMPK pathway, which increases cellular glucose uptake and supports metabolic homeostasis.
Under stress (exercise, low nutrients), MOTS-c can move to the nucleus and influence expression of stress-response genes.

Why Researchers Use It

To study insulin sensitivity, glucose handling, and mitochondrial stress signaling.
To model exercise-mimetic effects and energy-management pathways.
To explore healthy aging hypotheses tied to cellular stress resistance.

Key Studies — What Was Tested, What Changed, Why It Matters

Metabolic homeostasis & insulin sensitivity (foundational work)

What was tested: MOTS-c exposure in cell and animal models tracking glucose uptake, insulin response, and weight trends.
What changed: Improved insulin sensitivity, better glucose tolerance, and protection against diet-induced weight gain in rodent models.
Why it matters: Establishes MOTS-c as a tool for studying AMPK-centric energy regulation rather than direct hormone replacement.

Stress-response gene programs (nuclear translocation)

What was tested: Cellular stress conditions (e.g., low glucose) and MOTS-c localization.
What changed: MOTS-c translocated to the nucleus and engaged NRF2/ARE-linked antioxidant and stress-adaptation genes.
Why it matters: Shows how a mitochondrial peptide can coordinate nuclear gene expression during stress, bridging mitochondria–nucleus communication.

Human-relevance signals (observational)

What was tested: Associations between circulating or tissue MOTS-c and markers like insulin resistance, fat mass, and age.
What changed: Reports link MOTS-c levels to metabolic health and age-related trends (direction and magnitude vary by cohort).
Why it matters: Guides sample timing and cohort selection in translational designs; still requires controlled interventional work for causality.

Potential Research Applications

Metabolic Models

Glucose uptake and insulin-signaling assays
AMPK activation and downstream readouts

Exercise & Stress Biology

Exercise-mimetic pathways and mitochondrial stress tests
NRF2/ARE antioxidant-gene programs

Healthy Aging Hypotheses

Cellular resilience and oxidative-stress models
Adiposity distribution and metabolic flexibility

Synergistic Peptides (for Study Design)

Semaglutide (GLP-1)

Why pair: Incretin pathway for appetite/glucose control complements MOTS-c’s AMPK-centric energy signaling.
Angle: Combined readouts: food intake, glycemia, and AMPK markers.

Tirzepatide (GLP-1 + GIP)

Why pair: Dual incretin model to compare single vs dual hormone signaling layered on AMPK activation.
Angle: Insulin sensitivity, lipid panels, and body-composition trends.

AOD-9604 (hGH fragment 176–191)

Why pair: Focuses on fat-metabolism pathways; useful alongside AMPK signaling.
Angle: Lipolysis + glucose-uptake panels with imaging-based adiposity endpoints.

Design Notes

Pre-define fasting/feeding windows—metabolic endpoints are timing-sensitive.
Capture both acute (minutes–hours) AMPK readouts and chronic (weeks) composition markers.
Document vehicle, pH, light, and freeze–thaw cycles; small handling shifts can move results.

Known Concerns (Context)

Assay design: AMPK signaling is highly context-dependent; standardize stressors, temperature, and nutrient media.
Translation: Strong preclinical signals exist; human-interventional data are still developing across indications.
General: Sold for laboratory research use only; not for human/medical/veterinary use.

Follow institutional SOPs for metabolic-pathway peptides and mitochondrial-stress assays.

Specifications & Handling

Form: Lyophilized powder (lot-coded)
Purity: ≥ 99% (HPLC/MS verified)
Storage: ≤ −20 °C; protect from light/moisture

In solution: Aliquot promptly; avoid repeat freeze–thaw
Additives: None unless specified per lot
Packaging: Tamper-evident; research-only labeling

Regulatory & Use Notice

Sold for laboratory research use only. Not for human consumption, medical, or veterinary use. No human-use instructions are provided. Buyer is responsible for safe handling and regulatory compliance.

MOTS-c Peptide Research | Mitochondria-Derived Peptide | AMPK, Insulin Sensitivity & Stress-Response Studies

Keywords: MOTS-c peptide, mitochondrial-derived peptide, AMPK activation, insulin sensitivity, metabolic homeostasis, exercise mimetic, Base Peptides.