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

Narrative review of experimental and clinical studies

“The objective of the present paper is to offer an up‑to‑date (as of March 2026), comprehensive, and critical review of the potential roles of MOTS‑c in the pathophysiology and clinical dimensions of pulmonary diseases, particularly those characterized by well‑documented oxidative stress and prominent inflammation.”

Human patients with respiratory diseases and preclinical animal models

“Available experimental and clinical studies suggest that circulating MOTS-c levels are reduced in different forms of acute respiratory distress, while exogenous administration attenuates lung injury in preclinical models.”

Varies by cited study; specific examples include n=20 for asthma and 35 patients for lung cancer

“In a small cohort of patients with asthma (n = 20), reduced circulating MOTS‑c levels were observed [70]”

Not applicable to the review itself; cited studies range from acute interventions to chronic disease states

“The objective of the present paper is to offer an up‑to‑date (as of March 2026), comprehensive, and critical review of the potential roles of MOTS‑c in the pathophysiology and clinical dimensions of pulmonary diseases, particularly those characterized by well‑documented oxidative stress and prominent inflammation.”

Circulating MOTS-c levels are reduced in chronic respiratory diseases such as COPD, OSA, and asthma

“In contrast, chronic respiratory diseases such as chronic obstructive pulmonary disease, obstructive sleep apnea, and asthma are characterized by decreased MOTS-c concentrations, reflecting severe mitochondrial dysfunction and reduced cytoprotective capacity.”

Exogenous MOTS-c administration attenuates lung injury and inflammation in preclinical models

“Available experimental and clinical studies suggest that circulating MOTS-c levels are reduced in different forms of acute respiratory distress, while exogenous administration attenuates lung injury in preclinical models.”

MOTS-c levels are elevated in lung cancer patients, potentially related to NRF2-mediated antioxidant responses

“Preliminary observations suggest increased MOTS-c levels in lung cancer, potentially related to NRF2-mediated antioxidant responses, although these findings require further validation.”

Clinical evidence is preliminary, and technical issues regarding assay standardization and stability remain unresolved

“Although clinical evidence remains preliminary, mechanistic studies in animal models provide highly promising insights.”