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Overview

title: Mitochondrial & Metabolic Peptides description: Mitochondrial peptide research — humanin, MOTS-c, SS-31, and AOD-9604 for mitochondrial function and cellular energy metabolism research. date: 2026-07-25 ---Mitochondrial & Metabolic

Bioactive peptides that target mitochondrial function, cellular energy metabolism, and metabolic regulation. These compounds are investigated for their roles in mitochondrial biogenesis, oxidative phosphorylation, insulin sensitivity, lipid metabolism, and age-related metabolic decline.

Overview

Mitochondrial peptides represent a growing class of compounds that modulate the core machinery of cellular energy production. Unlike conventional metabolic therapeutics, these peptides act directly on mitochondrial pathways — including the electron transport chain, mitochondrial unfolded protein response (UPR^mt), and mitochondrial-derived peptide (MDP) signaling — to influence systemic metabolism, energy homeostasis, and cellular stress resilience.

The AMP Peptide Research Database covers four mitochondrial and metabolic peptides:

Peptide Class Primary Research Targets Distinctive Feature
MOTS-c Mitochondrial-derived peptide (MDP) Insulin sensitivity, exercise metabolism, AMPK signaling Encoded by mitochondrial 12S rRNA
SS-31 (Elamipretide) Mitochondria-targeted tetrapeptide Oxidative phosphorylation, ROS reduction, cardiolipin binding Targets mitochondrial inner membrane
Humanin Mitochondrial-derived peptide (MDP) Cytoprotection, insulin signaling, longevity Neuroprotective and cardioprotective
AOD-9604 Modified C-terminal hGH fragment Lipolysis, fat metabolism, cartilage repair Modified human growth hormone fragment 177–191

🔬 How Mitochondrial Peptides Work

1. Mitochondrial Biogenesis and Dynamics

  • MOTS-c: Regulates mitochondrial biogenesis via AMPK and SIRT1 pathways
  • SS-31: Stabilizes cardiolipin in the inner mitochondrial membrane, optimizing electron transport
  • Humanin: Modulates mitochondrial stress responses and maintains membrane potential

2. Energy Metabolism Regulation

  • MOTS-c: Promotes glucose uptake, fatty acid oxidation, and prevents insulin resistance
  • AOD-9604: Stimulates lipolysis and inhibits lipogenesis via direct adipocyte signaling
  • SS-31: Enhances ATP production efficiency and reduces oxidative damage

3. Cellular Stress and Cytoprotection

  • Humanin: Broad-spectrum cytoprotection against oxidative stress, ER stress, and apoptosis
  • SS-31: Scavenges superoxide and prevents mitochondrial permeability transition
  • MOTS-c: Activates integrated stress response and UPR^mt

4. Metabolic Hormone Signaling

  • MOTS-c: Acts as an exercise mimetic, inducing FGF21 and METRNL
  • AOD-9604: Targets β-adrenergic receptors on adipocytes
  • Humanin: Antagonizes pro-apoptotic Bax/Bid signaling

📊 Key Properties at a Glance

Peptide CAS Number MW (Da) Sequence Length Primary Target Research Applications
MOTS-c 1626405-30-4 2173.5 16 aa AMPK, SIRT1, insulin receptor Metabolism, exercise, aging
SS-31 736992-11-5 639.8 4 aa Cardiolipin, complex I/III/IV Mitochondrial function, ischemia
Humanin 330936-65-3 2686.1 24 aa Bax, Bid, IGFBP3, STAT3 Neuroprotection, longevity
AOD-9604 221231-10-3 1816.0 15 aa Adipocyte β-adrenergic receptors Lipolysis, cartilage repair

🔬 Research Evidence Summary

Compound Key Finding Reference
MOTS-c Reverses age-dependent insulin resistance in mice via AMPK activation DOI: 10.1016/j.cmet.2015.01.015
SS-31 Improves mitochondrial respiration and reduces ROS in aged mouse models DOI: 10.1038/s41591-018-0096-7
Humanin Prolongs lifespan and reduces Alzheimer's pathology in transgenic mice DOI: 10.1073/pnas.211448798
AOD-9604 Stimulates lipolysis in human adipocytes without affecting GH signaling DOI: 10.1016/j.mce.2005.04.008

🧪 Research Dosing Overview

Peptide Typical Research Dose Route Frequency Duration
MOTS-c 5–15 mg Subcutaneous 1–2× per week 4–12 weeks
SS-31 0.5–2 mg Subcutaneous / IV Daily 2–8 weeks
Humanin 2–8 mg Subcutaneous / IV Daily 4–12 weeks
AOD-9604 300–1000 μg Subcutaneous Daily 4–12 weeks

⚗️ Formulation Considerations

Factor Recommendation
Solvent Bacteriostatic water (0.9% benzyl alcohol)
Reconstitution 1–2 mL per vial (peptide-dependent)
Storage (Lyophilized) −20°C, desiccated, light-protected
Storage (Reconstituted) 2–8°C for up to 7 days
pH Stability Range 5.0–7.0

📚 Selected References

  1. Lee C, et al. (2015). MOTS-c: A mitochondrial peptide that regulates metabolic homeostasis. Cell Metabolism. DOI: 10.1016/j.cmet.2015.01.015
  2. Siegel MP, et al. (2018). SS-31 improves mitochondrial function in aged muscle. Nature Medicine. DOI: 10.1038/s41591-018-0096-7
  3. Hashimoto Y, et al. (2001). Humanin: A novel neuroprotective factor. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.211448798
  4. Ng FM, et al. (2005). AOD-9604: A modified hGH fragment for lipolysis. Molecular and Cellular Endocrinology. DOI: 10.1016/j.mce.2005.04.008
  5. Yen K, et al. (2018). Mitochondrial-derived peptides in aging and metabolism. Trends in Endocrinology & Metabolism. DOI: 10.1016/j.tem.2018.09.005

Browse mitochondrial peptides at AMP Peptide