SS-31 (Elamipretide) — Research Overview

Introduction

SS-31 (also known as Elamipretide, MTP-131, or Bendavia) is a synthetic
mitochondria-targeting tetrapeptide designed to selectively bind and stabilize cardiolipin on the
inner mitochondrial membrane. Research has focused heavily on its potential to improve ATP production, reduce
oxidative stress, support mitochondrial structure, and enhance cellular resilience in high-demand or aging tissues.

Its unique intracellular mechanism distinguishes SS-31 from traditional receptor-based peptides, positioning it
as a leading molecule in mitochondrial biology, metabolic research, cardiovascular studies, neuroprotection,
and muscle-performance science.

Chemical Characteristics

CAS #: 736992-21-5
Formula: C₃₂H₄₉N₉O₅
M.W.: 639.8 g/mol

Mechanisms of Action

1. Cardiolipin Binding & Mitochondrial Stabilization

SS-31 selectively binds cardiolipin within the inner mitochondrial membrane, helping to stabilize electron-transport
chain supercomplexes, reduce electron leakage, maintain membrane curvature, and improve oxidative phosphorylation efficiency.

2. Reduction of Mitochondrial ROS

By optimizing ETC function, SS-31 may lower mitochondrial ROS production through improved electron flow, stabilized
membrane potential, and prevention of cardiolipin peroxidation.

3. Enhancement of ATP Production

SS-31 is widely studied for its potential to improve ATP output by supporting efficient ETC activity, optimizing
mitochondrial respiration, and enhancing energy availability during cellular stress.

4. Anti-Apoptotic & Cytoprotective Actions

Research indicates SS-31 may reduce release of pro-apoptotic factors, improve mitochondrial resilience under injury,
and enhance cell survival in stressed, inflamed, or oxygen-deprived tissues.

Research Applications

1. Mitochondrial Dysfunction & Aging

SS-31 is a major molecule in mitochondrial-aging research due to its potential to restore membrane potential, improve
bioenergetic capacity, reduce oxidative stress, and normalize mitochondrial dynamics.

2. Cardiovascular Research

Cardiac muscle is highly mitochondrial, making SS-31 a strong research candidate for ischemia/reperfusion injury,
cardiac energetics, endothelial dysfunction, and ATP depletion in stressed cardiac tissue.

3. Neuroprotection & Cognitive Health

SS-31 is studied in neural models for its ability to reduce neuronal oxidative stress, support mitochondrial transport,
promote synaptic resilience, and protect against age-related neurodegeneration.

4. Skeletal Muscle Function & Performance

Research indicates SS-31 may influence muscle fatigue resistance, exercise-induced mitochondrial stress, age-related
muscle decline, and ATP availability during physical activity.

5. Systemic Metabolic & Organ Protection

SS-31 has been evaluated in studies of kidney ischemia, liver oxidative stress, diabetic mitochondrial dysfunction,
and whole-body energy imbalance.

Practical Considerations in Research Models

• Rapidly permeates cells and accumulates in mitochondria
• Effects are dose-dependent and time-dependent
• Common endpoints include ATP output, ROS levels, membrane potential, and mitochondrial stability
• Outcomes vary by tissue type, metabolic stress level, and mitochondrial density

Conclusion

SS-31 (Elamipretide) is a specialized mitochondrial-targeting tetrapeptide extensively studied for enhancing ATP
production, reducing oxidative stress, stabilizing mitochondrial membranes, and improving cellular resilience. Its
cardiolipin-binding mechanism sets it apart from conventional peptides, making it a leading compound in research
focused on aging, metabolic balance, cardiac energetics, neuroprotection, and muscle performance.