SS-31 (Elamipretide)

Key Benefits#

• Restores mitochondrial function and ATP production
• Protects inner mitochondrial membrane cardiolipin
• Reduces mitochondrial reactive oxygen species (ROS)
• Improves exercise capacity and reduces fatigue
• Cardioprotective — studied in heart failure trials
• Renoprotective — reduces ischemic kidney injury
• Anti-aging via mitochondrial preservation
• Potential in neurodegenerative disease prevention

Mechanism of Action#

SS-31 is a cell-permeable tetrapeptide that selectively concentrates 1000-fold in the inner mitochondrial membrane due to its alternating aromatic-cationic structure. It binds cardiolipin, a phospholipid critical for the electron transport chain, protecting it from peroxidation and restoring mitochondrial cristae architecture. This reactivates cytochrome c and Complex I/IV activity, restoring ATP production and reducing mitochondrial ROS. It has undergone Phase II clinical trials for heart failure.

Dosing Protocols#

Side Effects#

• Injection site irritation
• Nausea (rare)
• Generally well-tolerated in clinical trials

Contraindications#

Pregnancy or breastfeeding. Limited long-term human safety data outside clinical trials.

Storage#

Lyophilized powder: store at −20°C. Reconstituted: refrigerate at 2–8°C, use within 14 days.

Featured In Stacks#

1. 1.
   Endothelial Glycocalyx Degradation as a Mediator of Neuroinflammation and Cognitive Impairment in Aged Rats: Protective Role of SS-31

   Kan MH, Liu Y, Meng FQ, Fan L, Wu Y, Wang TL · Molecular neurobiology · 2025PubMed Verified

2. 2.
   Mitochondrial dysfunction drives age-related degeneration of the thoracic aorta

   Dhanekula AS, Harrison BR, Pharaoh G, Mattson-Hughes A, Tarantini S, Stuppard R et al. · GeroScience · 2025PubMed Verified

3. 3.
   Therapeutic Approaches Involving Mitochondria in the Treatment of Acute Kidney Injury

   Patel PS, Pabla NS, Bajwa A · Seminars in nephrology · 2026ReviewPubMed Verified

4. 4.
   Mitochondrial-Targeted Protective Potential of Elamipretide for the In Vitro Production of Porcine Embryos

   Nguyen ST, Otoi T, Namula Z, Widodo OS, Tharasanit T, Chatdarong K et al. · Animals : an open access journal from MDPI · 2025PubMed Verified

5. 5.
   Elamipretide in the Management of Barth Syndrome: Current Evidence and a Case Report

   Jacob N, Schecter D, Marshall M, Bansal N, Lamour J, Vernon H et al. · Molecular genetics and metabolism · 2025Case ReportPubMed Verified

6. 6.
   Mitochondrial Dysfunction Drives Age-Related Degeneration of the Thoracic Aorta

   Dhanekula AS, Harrison BR, Pharaoh G, Mattson-Hughes A, Tarantini S, Stuppard R et al. · bioRxiv : the preprint server for biology · 2025PubMed Verified

7. 7.
   Environmental enrichment highlights mitochondrial inner membrane function as a therapeutic target for sepsis-associated encephalopathy

   Wang SX, Yin XY, Jian JX, Ji MH, Yang JJ, Shen JC · Brain research · 2025PubMed Verified

8. 8.
   Acute mitochondrial reactive oxygen species emissions drive mitochondrial dysfunction after traumatic muscle injury in male mice

   Heo J, Miller DL, Hoffman JR, Oberholtzer E, Castelli KM, Sparagna GC et al. · American journal of physiology. Cell physiology · 2025PubMed Verified

9. 9.
   Innovative technologies for the treatment of dry age-related macular degeneration (AMD) - modern therapeutic perspectives and their future

   Ciszewski P, Drelichowska A, Pikor D, Wiśniewska E, Azierski M · Romanian journal of ophthalmology · 2025ReviewPubMed Verified

10. 10.
    SS-31: A promising therapeutic agent against bleomycin-induced pulmonary fibrosis in Mice

    Gu Q, Wang Y, Zhang H, Yang W, Meng X, Zhao M · PloS one · 2025PubMed Verified

11. 11.
    Mitochondrial Cardiolipin-Targeted Tetrapeptide, SS-31, Exerts Neuroprotective Effects Within In Vitro and In Vivo Models of Spinal Cord Injury

    Ravenscraft B, Lee DH, Dai H, Watson AL, Aparicio GI, Han X et al. · International journal of molecular sciences · 2025PubMed Verified

12. 12.
    Aging, mitochondrial dysfunction, and cerebral microhemorrhages: a preclinical evaluation of SS-31 (elamipretide) and development of a high-throughput machine learning-driven imaging pipeline for cerebromicrovascular protection therapeutic screening

    Patai R, Patel K, Csik B, Gulej R, Nagaraja RY, Nagy D et al. · GeroScience · 2025PubMed Verified

13. 13.
    Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential

    Tung C, Varzideh F, Farroni E, Mone P, Kansakar U, Jankauskas SS et al. · International journal of molecular sciences · 2025ReviewPubMed Verified

14. 14.
    Cadmium-cardiolipin disruption of respirasome assembly and redox balance through mitochondrial membrane rigidification

    Romanova N, Sule K, Issler T, Hebrok D, Persicke M, Thévenod F et al. · Journal of lipid research · 2025PubMed Verified

15. 15.
    SS-31@Fer-1 Alleviates ferroptosis in hypoxia/reoxygenation cardiomyocytes via mitochondrial targeting

    Zheng H, Ou J, Han H, Lu Q, Shen Y · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025PubMed Verified

16. 16.
    Reprogramming of Treg cell-derived small extracellular vesicles effectively prevents intestinal inflammation from PANoptosis by blocking mitochondrial oxidative stress

    Gong W, Liu Z, Wang Y, Huang W, Yang K, Gao Z et al. · Trends in biotechnology · 2025PubMed Verified

17. 17.
    Post-sepsis chronic muscle weakness can be prevented by pharmacological protection of mitochondria

    Kingren MS, Keeble AR, Galvan-Lara AM, Ogle JM, Ungvári Z, St Clair DK et al. · Molecular medicine (Cambridge, Mass.) · 2024PubMed Verified

18. 18.
    New insight for SS‑31 in treating diabetic cardiomyopathy: Activation of mitoGPX4 and alleviation of mitochondria‑dependent ferroptosis

    Xiong L, Hu H, Zhu F, Shi H, Fan X, Pan S et al. · International journal of molecular medicine · 2024PubMed Verified

19. 19.
    SS-31 mitigates oxidative stress and restores mitochondrial function in cigarette smoke-damaged oral epithelial cells via PINK1-mediated mitophagy

    Ye P, Liu H, Qin Y, Li Z, Huang Z, Bu X et al. · Chemico-biological interactions · 2024PubMed Verified

20. 20.
    SS-31 treatment ameliorates cardiac mitochondrial morphology and defective mitophagy in a murine model of Barth syndrome

    Russo S, De Rasmo D, Rossi R, Signorile A, Lobasso S · Scientific reports · 2024PubMed Verified

21. 21.
    Skeletal muscle mitochondrial dysfunction mediated by Pseudomonas aeruginosa quorum-sensing transcription factor MvfR: reversing effects with anti-MvfR and mitochondrial-targeted compounds

    Aggarwal S, Singh V, Chakraborty A, Cha S, Dimitriou A, de Crescenzo C et al. · mBio · 2024PubMed Verified

22. 22.
    Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage

    Xia Y, Zhang Y, Du Y, Wang Z, Cheng L, Du Z · Journal of nanobiotechnology · 2024PubMed Verified

23. 23.
    Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice

    Zhang YM, Wang YT, Wei RM, Li XY, Luo BL, Zhang JY et al. · Brain and behavior · 2024PubMed Verified

24. 24.
    Effect of Elamipretide on the Vitrification of Mouse Ovarian Tissue by Freezing

    Yao X, Lu Q, Wu Y, Liu J, Liu N, Huang X et al. · Biopreservation and biobanking · 2024PubMed Verified

25. 25.
    Mitochondria-targeting peptide SS-31 attenuates ferroptosis via inhibition of the p38 MAPK signaling pathway in the hippocampus of epileptic rats

    Liu X, Wang FY, Chi S, Liu T, Yang HL, Zhong RJ et al. · Brain research · 2024PubMed Verified

26. 26.
    Mitochondria-targeted reactive oxygen species blockor SS-31 blocks hepatic stellate cell activation and alleviates hepatic fibrosis by regulating NLRP3 inflammasomes

    Liu L, Wei Y, Xie N, Cai H, Lin Y · Cellular and molecular biology (Noisy-le-Grand, France) · 2024PubMed Verified

27. 27.
    SS-31 inhibits mtDNA-cGAS-STING signaling to improve POCD by activating mitophagy in aged mice

    Ji Y, Ma Y, Ma Y, Wang Y, Zhao X, Jin D et al. · Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024PubMed Verified

28. 28.
    Doxycycline induces mitochondrial dysfunction in aortic smooth muscle cells

    Yap C, Wanga S, Wüst RCI, van Os BW, Pijls MME, Keijzer S et al. · Vascular pharmacology · 2024PubMed Verified

29. 29.
    Application research of novel peptide mitochondrial-targeted antioxidant SS-31 in mitigating mitochondrial dysfunction

    Du X, Zeng Q, Luo Y, He L, Zhao Y, Li N et al. · Mitochondrion · 2024ReviewPubMed Verified

30. 30.
    Age-related changes of skeletal muscle metabolic response to contraction are also sex-dependent

    Garibotti MC, Khajehzadehshoushtar S, Andrews NJ, Malekzadeh R · The Journal of physiology · 2025PubMed Verified

31. 31.
    Elamipretide(SS-31) Attenuates Idiopathic Pulmonary Fibrosis by Inhibiting the Nrf2-Dependent NLRP3 Inflammasome in Macrophages

    Nie Y, Li J, Zhai X, Wang Z, Wang J, Wu Y et al. · Antioxidants (Basel, Switzerland) · 2023PubMed Verified

32. 32.
    The mitochondrially targeted peptide elamipretide (SS-31) improves ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT)

    Pharaoh G, Kamat V, Kannan S, Stuppard RS, Whitson J, Martín-Pérez M et al. · GeroScience · 2023PubMed Verified

33. 33.
    Elamipretide alleviates pyroptosis in traumatically injured spinal cord by inhibiting cPLA2-induced lysosomal membrane permeabilization

    Zhang H, Chen Y, Li F, Wu C, Cai W, Ye H et al. · Journal of neuroinflammation · 2023PubMed Verified

34. 34.
    Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice

    Russo S, De Rasmo D, Signorile A, Corcelli A, Lobasso S · Scientific reports · 2022PubMed Verified

35. 35.
    Aging Increases Susceptibility to Develop Cardiac Hypertrophy following High Sugar Consumption

    Valencia AP, Whitson JA, Wang S, Nguyen L, den Hartigh LJ, Rabinovitch PS et al. · Nutrients · 2022PubMed Verified

36. 36.
    Long-term treatment with Elamipretide enhances healthy aging phenotypes in mice

    Nickel K, Zhu L, Mangalindan R, Snyder JM, Tucker M, Whitson J et al. · Aging pathobiology and therapeutics · 2022PubMed Verified

37. 37.
    SS-31 as a Mitochondrial Protectant in the Treatment of Tendinopathy: Evaluation in a Murine Supraspinatus Tendinopathy Model

    Zhang X, Bowen E, Zhang M, Szeto HH, Deng XH, Rodeo SA · The Journal of bone and joint surgery. American volume · 2022PubMed Verified

38. 38.
    Mitochondria-Related Ferroptosis Drives Cognitive Deficits in Neonatal Mice Following Sevoflurane Administration

    Zhang P, Chen Y, Zhang S, Chen G · Frontiers in medicine · 2022PubMed Verified

39. 39.
    Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds

    Mitchell W, Tamucci JD, Ng EL, Liu S, Birk AV, Szeto HH et al. · eLife · 2022PubMed Verified

40. 40.
    Evaluation of SS-31 as a Potential Strategy for Tendinopathy Treatment: An In Vitro Model

    Zhang X, Zhang Y, Zhang M, Nakagawa Y, Caballo CB, Szeto HH et al. · The American journal of sports medicine · 2022PubMed Verified

41. 41.
    A ROS-Responsive Liposomal Composite Hydrogel Integrating Improved Mitochondrial Function and Pro-Angiogenesis for Efficient Treatment of Myocardial Infarction

    Zheng Z, Lei C, Liu H, Jiang M, Zhou Z, Zhao Y et al. · Advanced healthcare materials · 2022PubMed Verified

42. 42.
    Age-related disruption of the proteome and acetylome in mouse hearts is associated with loss of function and attenuated by elamipretide (SS-31) and nicotinamide mononucleotide (NMN) treatment

    Whitson JA, Johnson R, Wang L, Bammler TK, Imai SI, Zhang H et al. · GeroScience · 2022PubMed Verified

43. 43.
    Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration

    Nhu NT, Xiao SY, Liu Y, Kumar VB, Cui ZY, Lee SD · Frontiers in integrative neuroscience · 2021ReviewPubMed Verified

44. 44.
    Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD)

    Nashine S · Cells · 2021ReviewPubMed Verified

45. 45.
    Elamipretide (SS-31) treatment attenuates age-associated post-translational modifications of heart proteins

    Whitson JA, Martín-Pérez M, Zhang T, Gaffrey MJ, Merrihew GE, Huang E et al. · GeroScience · 2021PubMed Verified

46. 46.
    Pharmacologic approaches to prevent skeletal muscle atrophy after spinal cord injury

    Otzel DM, Kok HJ, Graham ZA, Barton ER, Yarrow JF · Current opinion in pharmacology · 2021ReviewPubMed Verified

47. 47.
    Mitochondrial dysfunction and beneficial effects of mitochondria-targeted small peptide SS-31 in Diabetes Mellitus and Alzheimer's disease

    Ding XW, Robinson M, Li R, Aldhowayan H, Geetha T, Babu JR · Pharmacological research · 2021ReviewPubMed Verified

48. 48.
    Mitochondrial-Targeting Antioxidant SS-31 Suppresses Airway Inflammation and Oxidative Stress Induced by Cigarette Smoke

    Yang DQ, Zuo QN, Wang T, Xu D, Lian L, Gao LJ et al. · Oxidative medicine and cellular longevity · 2021PubMed Verified

49. 49.
    Role of AQP3 in the Vascular Leakage of Sepsis and the Protective Effect of Ss-31

    Zhang J, Wang P, Wu Y, Zhu Y, Peng XY, Xiang XM et al. · Journal of cardiovascular pharmacology · 2021PubMed Verified

50. 50.
    SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization

    Shang L, Ren H, Wang S, Liu H, Hu A, Gou P et al. · Oxidative medicine and cellular longevity · 2021PubMed Verified