Mots-C
Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1, Mitochondrial-derived peptide MOTS-c
MOTS-c attenuates airway barrier dysfunction in allergic asthma by inhibiting epithelial apoptosis via Nrf2 pathway.
Zhang. Wenlong W; Li. Shengpeng S; Zhang. Yanli Y; Wu. Yaxian Y; Chen. Dan D; Pang. Qingfeng Q; Han. Shuguang S
Key Findings
- Asthma patients have reduced serum MOTS‑c compared to healthy people
- Supplementing MOTS‑c in mice reduces lung tissue damage, inflammation, and oxidative stress from allergen exposure
- MOTS‑c preserves airway epithelial barrier and mitochondrial function by activating Nrf2 and preventing apoptosis
Practical Outcomes
- While the findings are promising, MOTS‑c isn’t yet available as a supplement or drug for self‑use. Biohackers should wait for clinical trials before considering it, but the study highlights the potential of targeting the Nrf2 pathway or naturally boosting MOTS‑c (e.g., through exercise) to support airway health.
Summary
A small protein called MOTS‑c is found at lower levels in people with asthma. In mouse and cell experiments, giving extra MOTS‑c protected lung cells from damage caused by allergens, reduced inflammation and oxidative stress, and kept the airway barrier intact by activating the Nrf2 pathway that prevents cell death. These results suggest MOTS‑c could be a future therapy for allergic asthma, but it’s still early‑stage research.
Abstract
Allergic asthma (AA), a severe chronic respiratory disease of chronic airway inflammation, is characterized by bronchial epithelial barrier dysfunction. The MOTS-c/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a protective role in various diseases by reducing inflammatory responses. This study aimed to evaluate the effects of MOTS-c on airway epithelial barrier function in AA. MOTS-c levels in the serum of patients with asthma and healthy volunteers were measured by ELISA. C57BL/6 and Nrf2-knockout (Nrf2<sup>-/-</sup>) mice were stimulated with house dust mites (HDM) to establish an asthma model. Lung tissue injury and mitochondrial function were assessed using hematoxylin and eosin, immunofluorescence, and immunohistochemistry staining. BEAS-2B cells were pretreated using 10 μM MOTS-c for 2 h and then treated with HDM (1 μM) for 24 h. The epithelial barrier and mitochondrial function were detected through western blot and real-time quantitative polymerase chain reaction, respectively. MOTS-c levels were lower in the serum of patients with asthma than in that of healthy volunteers. Exogenous supplementation of MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by HDM. However, MOTS-c reversed the barrier function and mitochondrial damage in AA mice. Furthermore, MOTS-c significantly inhibited inflammation, oxidative stress, and mitochondrial damage in HDM-stimulated BEAS-2B cells. Mechanistically, MOTS-c attenuates airway barrier damage in AA by inhibiting bronchial epithelial apoptosis via the Nrf2 pathway. MOTS-c alleviated AA by attenuating airway barrier dysfunction through an Nrf2-dependent mechanism. Therefore, MOTS-c may potentially act as a novel protective agent against AA.
Study Information
pubmed
2025
2025-06-04T00:00:00.000Z
10.1016/j.intimp.2025.115014
2
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