MOTS-c preserves mitochondrial subpopulation bioenergetics and genome integrity to attenuate cardiac ischemia reperfusion injury

In isolated rat hearts subjected to ischemia and reperfusion, MOTS-c treatment preserved mitochondrial function and reduced injury, leading to better cardiac recovery. The study provides evidence that this mitochondrial-derived peptide can protect both subsarcolemmal and interfibrillar mitochondria.

Journal article — ex vivo Langendorff perfused rat heart study. Population: female Wistar rat hearts subjected to global ischemia-reperfusion. Sample size: 6 hearts per group. Follow-up: 30 min ischemia followed by 60 min reperfusion. Interventions: MOTS-c 53 µM administered before ischemia or at reperfusion onset.

In untreated hearts, ischemia-reperfusion significantly impaired cardiac mechanical recovery, increased oxidative stress, reduced electron transport chain and dehydrogenase enzyme activities, disrupted mitochondrial membrane potential, and decreased mtDNA copy number and mitochondrial regulatory gene expression. MOTS-c (53 µM) improved post-ischemic mechanical recovery and attenuated oxidative stress. It also partially preserved mitochondrial enzyme activities and membrane potential, and mitigated reductions in mtDNA copy number and mitochondrial gene expression. Protective effects were observed in both subsarcolemmal and interfibrillar mitochondria, though responses varied across parameters.

Researchers studying MOTS-c will find evidence that MOTS-c can protect mitochondrial bioenergetics and mtDNA integrity in cardiac ischemia-reperfusion injury, extending its known metabolic roles to the heart. It does not establish the signaling mechanism or clinical utility in humans; no in vivo data or dose-response testing is reported.

Key findings

• MOTS-c at 53 µM improved post-ischemic cardiac mechanical recovery compared with untreated ischemia-reperfusion hearts.
• MOTS-c attenuated oxidative stress and partially preserved mitochondrial enzyme activities and membrane potential.
• MOTS-c mitigated reductions in mtDNA copy number and mitochondrial regulatory gene expression following ischemia-reperfusion.
• Protective effects were seen in both subsarcolemmal and interfibrillar mitochondrial populations, with variation across parameters.
• Ischemia-reperfusion alone significantly impaired cardiac mechanical recovery, increased oxidative stress, and disrupted mitochondrial bioenergetics.

Limitations

• Ex vivo Langendorff model, not an in vivo or clinical study
• Single dose of MOTS-c (53 µM) tested, without dose-response analysis
• Only female Wistar rats were used
• Underlying signaling mechanisms were not validated

The record

• Journal: Molecular biology reports 53(1): 873
• Published: 2026-06-02
• PMID: 42228044 — DOI: 10.1007/s11033-026-12064-7
• MeSH terms: Myocardium, Mitochondria, Mitochondria, Heart, Animals, Rats, Rats, Wistar, Myocardial Reperfusion Injury, Mitochondrial Proteins, DNA, Mitochondrial, Energy Metabolism, Oxidative Stress, Female, Membrane Potential, Mitochondrial
• Author countries: India

Peptide profiles: MOTS-c.

All indexed evidence: MOTS-c trials & papers.

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