Overview
SS-31, also known as Elamipretide or the Szeto-Schiller peptide, is a synthetic tetrapeptide originally developed by researchers Hazel Szeto and Peter Schiller as part of a class of mitochondria-targeting compounds. It belongs to a category of peptides specifically designed to concentrate within the inner mitochondrial membrane, where researchers believe it may interact with cardiolipin, a key phospholipid involved in mitochondrial energy production. Because of this targeted mechanism, SS-31 has attracted significant scientific interest as a tool for studying mitochondrial function, oxidative stress, and cellular energy dynamics in preclinical research settings. Studies have explored its potential role in models involving neurological injury, cardiac stress, and other conditions where mitochondrial dysfunction is thought to play a central role. SS-31 is intended strictly for laboratory and research purposes and is not approved for human use or consumption.
Research & Bioactivity
Researchers have studied SS-31, also known as elamipretide, primarily in the context of mitochondrial biology, with a particular focus on how this peptide interacts with the inner mitochondrial membrane to influence bioenergetics and oxidative stress responses. In animal models of spinal cord injury, studies have examined whether SS-31 administration is associated with preserved mitochondrial function, reduced apoptosis, and changes in neurological recovery outcomes. Research has also investigated the peptide's potential relevance to lung injury, with neonatal murine models of hyperoxia-induced bronchopulmonary dysplasia serving as an experimental platform for exploring mitochondrial oxidative phosphorylation. Additional studies have looked at hepatic ischemia-reperfusion injury, where excessive mitochondrial reactive oxygen species production is a central area of interest, and SS-31 has been included in comparative research examining mitochondria-targeted interventions. Researchers have further explored SS-31 in the context of sepsis-associated encephalopathy, where mitochondrial dysfunction and neuroinflammation are under investigation as interconnected pathological mechanisms.
Published Research
Effect of mitochondrial dysfunction on scar formation after spinal cord injury.
Zhang Y, Jin Z, Ning B — 2026
Spinal cord injury (SCI) triggers a cascade of primary and secondary pathological events that culminate in the formation of glial and fibrotic scars, which constitute a major barrier to axonal regeneration and functional recovery. Emerging evidence highlights mitochondrial dysfunction as a central driver of this process. Mitochondria are essential for sustaining ATP production, maintaining redox balance, and regulating calcium homeostasis. Following SCI, direct mechanical disruption, oxidative stress, and calcium overload impair mitochondrial integrity, leading to energy metabolism collapse, excessive reactive oxygen species (ROS) accumulation, and disrupted mitochondrial dynamics. These alterations promote reactive gliosis, fibroblast activation, and maladaptive extracellular matrix deposition. Furthermore, defective mitophagy amplifies neuroinflammation and glial scar consolidation through the PINK1/Parkin and BNIP3/NIX pathways. Recent advances in mitochondrial-targeted therapies-including antioxidants (MitoQ, SS-31), metabolic modulators (AMPK agonists, NAD precursors), and strategies enhancing fusion or mitophagy-have demonstrated promising results in reducing scar formation and promoting neural repair. In addition, cutting-edge approaches such as mitochondrial transplantation, stem cell-derived mitochondrial transfer, and CRISPR-based mitochondrial gene editing provide new opportunities for restoring mitochondrial homeostasis. This review summarizes the multifaceted roles of mitochondrial dysfunction in SCI-induced scar formation and discusses novel therapeutic strategies targeting mitochondrial metabolism and dynamics to enhance neural regeneration.
Elamipretide (SS-31) promotes recovery by preserving mitochondrial bioenergetics and neural remodeling after spinal cord injury.
Song Z, Ban Z, Zhao H, Mei X — 2026
Spinal cord injury (SCI) induces secondary damage characterized by mitochondrial dysfunction, oxidative stress, and apoptosis, which collectively impede neurological recovery. Elamipretide (SS-31) is a mitochondria-targeting peptide with potential neuroprotective effects. Here, we investigated whether SS-31 improves functional outcomes after contusive SCI and explored associated mechanisms. In a mouse thoracic contusion model, SS-31 treatment significantly enhanced locomotor recovery and gait performance. Histological analyses showed reduced lesion pathology and increased neuronal preservation in the injured spinal cord. Early after injury, SS-31 attenuated apoptosis signaling, evidenced by reduced cleaved caspase-3 and Bax and increased Bcl-2. At the chronic stage, SS-31 was associated with diminished astrogliosis and enhanced markers of axonal and synaptic remodeling. In oxidatively stressed PC12 cells, SS-31 preserved mitochondrial membrane potential, reduced ROS accumulation, and supported oxidative phosphorylation-related protein integrity. Collectively, these findings suggest that SS-31 promotes recovery after SCI, potentially by mitigating early apoptotic injury and supporting mitochondrial homeostasis and neural remodeling.
SLC25A28 Ameliorates Hyperoxic Lung Injury by Improving Mitochondrial Oxidative Phosphorylation in Alveolar Epithelial Cells.
Lu T, Chen SQ, Li SH, Li SP, Wu YX, et al. — 2026
Mitochondrial dysfunction plays a central role in the pathogenesis of bronchopulmonary dysplasia (BPD). Solute carrier family 25 member 28 (SLC25A28) is an iron transporter located in the inner mitochondrial membrane. In this study, we aimed to explore the role and underlying molecular mechanisms of SLC25A28 in BPD. Hyperoxia (85% O) was used to establish a neonatal murine model of BPD, and mouse lung epithelial cells (MLE-12 cells) were used in vitro. SLC25A28 expression and activity were downregulated under hyperoxic conditions, both in vivo and in vitro. SLC25A28 overexpression restored hyperoxia-induced mitochondrial oxidative phosphorylation (OXPHOS) dysfunction, and further enhanced the proportion of Ki67-positive cells by 37% ( < 0.05) and increased migration by 33% ( < 0.01) in MLE-12 cells. In contrast, SLC25A28 knockdown exacerbated these impairments in MLE-12 cells, with reduced the proportion of Ki67 positive cells by 71% ( < 0.01) and a 35% reduction in the migration rate. SLC25A28 was also knocked down in vivo, which further aggravated alveolar simplification in BPD mice. Furthermore, the mitochondrial-targeted peptide SS-31 could potentially interact with SLC25A28 and preserve its protein abundance. SS-31 administration mitigated hyperoxia-induced alveolar simplification, with the radical alveolar count (RAC) increasing by 28% ( < 0.05) and the mean linear intercept (MLI) decreasing by 20% ( < 0.001). In summary, this study revealed that SLC25A28 ameliorated hyperoxic lung injury by improving mitochondrial OXPHOS in alveolar epithelial cells, suggesting that it may serve as a potential therapeutic target for BPD.
Mitochondrial dysfunction, neuroinflammation, and associated mechanisms in sepsis-associated encephalopathy: from pathogenesis to emerging therapeutics.
Shen Y, Ye XM, Li PY, Chen SL — 2026
Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis, leading to diffuse brain dysfunction, long-term cognitive deficits, and increased mortality. Its pathogenesis is complex, with mitochondrial dysfunction and neuroinflammation emerging as central, interconnected drivers. This review systematically elucidates the pathogenic crosstalk between these two processes. We detail how dysregulated mitochondrial dynamics (e.g., Drp1-mediated fission), impaired biogenesis (via the proliferator-activated receptor-gamma coactivator-1α axis), oxidative stress, and the activation of mitochondria-dependent cell death pathways (ferroptosis, pyroptosis) contribute to neuronal injury. Concurrently, microglial activation, particularly through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, creates a vicious cycle that exacerbates mitochondrial damage and synaptic loss. Furthermore, we summarize emerging therapeutic strategies that target this mitochondrial-neuroinflammatory axis, including molecular hydrogen, mitochondria-targeted peptides (), natural compounds, and specific inhibitors (e.g., , ). The integration of recent insights on the gut-brain axis and cerebral metabolomics further expands the therapeutic landscape. Ultimately, targeting this core axis offers a promising paradigm for developing effective interventions to improve neurological outcomes in septic patients.
Protective Effect of Mitochondria-Targeted Polydopamine Nanoparticles in Alleviating Hepatic Ischemia-Reperfusion Injury.
Huang Y, Cui X, You J, Xu L, Luo J, et al. — 2026
Hepatic ischemia-reperfusion injury (IRI), driven primarily by excessive mitochondrial reactive oxygen species (ROS) generation, is a major cause of liver dysfunction, graft failure, and postoperative complications. However, no pharmacological agents have been clinically approved for its prevention or treatment, and there is an urgent need for effective therapeutic strategies. In this study, we established a nanoplatform composed of PEGylated polydopamine nanoparticles modified with the mitochondrial-targeting peptide SS-31 (PPS NPs). SS-31 peptide modification confers PPS NPs with efficient mitochondrial-targeting capability, thereby restoring mitochondrial membrane potential and reducing ROS accumulation in the hypoxia/reoxygenation model. Furthermore, treatment with PPS NPs significantly mitigates liver injury, decreases inflammatory factor levels, and inhibits neutrophil recruitment in mice subjected to IRI. Transcriptome sequencing and metabolomics analyses indicate that PPS NPs can protect the liver from ischemia-reperfusion injury by preserving mitochondrial integrity, reducing ROS generation, and regulating arachidonic acid and glutathione metabolism. By preserving mitochondrial function, maintaining cellular redox homeostasis, and suppressing inflammatory cascades, PPS NPs ultimately inhibit mitochondria-dependent apoptosis and confer protection against liver IRI, providing a practical therapeutic strategy for hepatic IRI clinical management.