MOTS-c: How a secreted mitochondrial microprotein may become a potential treatment for inflammatory lung diseases

This review summarises evidence that the mitochondrial microprotein MOTS-c is lower in acute and chronic inflammatory lung diseases, while exogenous MOTS-c reduces lung injury in animal models. It suggests MOTS-c could be a biomarker and therapeutic candidate but stresses that clinical trials are needed.

Narrative review — review. Interventions: MOTS-c (exogenous administration); remote ischemic preconditioning.

The abstract reports that circulating MOTS-c is reduced in acute respiratory distress and that exogenous MOTS-c attenuates lung injury in preclinical models. Chronic respiratory diseases including COPD, obstructive sleep apnea, and asthma show decreased MOTS-c concentrations, reflecting severe mitochondrial dysfunction. Lung cancer shows increased MOTS-c levels, possibly via NRF2-mediated antioxidant responses, but this is preliminary. Remote ischemic preconditioning may act partly through MOTS-c release.

Researchers working on MOTS-c would use this review for a broad summary of its role in respiratory diseases and the direction of its dysregulation across conditions. The paper does not establish causal efficacy in humans, does not provide dosing data, and is not a systematic or quantitative synthesis.

Key findings

• Circulating MOTS-c levels are reduced in different forms of acute respiratory distress.
• Exogenous MOTS-c administration attenuates lung injury in preclinical models.
• Chronic obstructive pulmonary disease, obstructive sleep apnea, and asthma are characterized by decreased MOTS-c concentrations.
• Lung cancer is associated with increased MOTS-c levels, possibly via NRF2-mediated antioxidant responses, although these findings require further validation.
• Remote ischemic preconditioning appears to exert part of its protective effects through MOTS-c release.

Limitations

• Review article, not a new primary analysis.
• Authors state that well-designed translational and multicenter clinical studies are needed to determine whether MOTS-c modulation influences disease progression and outcomes.
• Lung cancer findings are preliminary and require further validation.
• Preclinical evidence for exogenous MOTS-c has not been confirmed in human trials.

The record

• Journal: Journal of translational medicine 24(1): 1031
• Published: 2026-06-04
• PMID: 42243958 — DOI: 10.1186/s12967-026-08398-2
• MeSH terms: Mitochondria, Animals, Humans, Lung Diseases, Inflammation, Mitochondrial Proteins, Micropeptides
• Author countries: Spain

Peptide profiles: MOTS-c.

All indexed evidence: MOTS-c trials & papers.

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