Mitochondria-Derived Peptide MOTS-c: Effects and Mechanisms Related to Stress, Metabolism and Aging
Open accessAbstract
MOTS-c is a peptide encoded by the short open reading frame of the mitochondrial 12S rRNA gene. It is significantly expressed in response to stress or exercise and translocated to the nucleus, where it regulates the expression of stress adaptation-related genes with antioxidant response elements (ARE). MOTS-c mainly acts through the Folate-AICAR-AMPK pathway, thereby influencing energy metabolism, insulin resistance, inflammatory response, exercise, aging and aging-related pathologies. Because of the potential role of MOTS-c in maintaining energy and stress homeostasis to promote healthy aging, especially in view of the increasing aging of the global population, it is highly pertinent to summarize the relevant studies. This review summarizes the retrograde signaling of MOTS-c toward the nucleus, the regulation of energy metabolism, stress homeostasis, and aging-related pathological processes, as well as the underlying molecular mechanisms.
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SIRT1 activators like resveratrol and NAD+ precursors have been shown to enhance mitochondrial biogenesis and oxidative metabolism, leading to improved muscle function and recovery.
“Similarly, SIRT1 activators like resveratrol and NAD+ precursors have been shown to enhance mitochondrial biogenesis and oxidative metabolism, leading to improved muscle function and recovery”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [118]
The Introduction section on pathways regulated by MOTS-c links SIRT1 and PGC-1α to mitochondrial biogenesis and respiratory function, and reports that the SIRT1 activator SRT1720 increased PGC-1α expression (page not provided). It does not report that resveratrol or NAD+ precursors improved muscle function or recovery; the muscle-performance findings in the Multiple functions section concern MOTS-c treatment instead. (LLM, conf=0.83)
Experimental — accuracy not yet measuredCurrent evidence on MOTS-c remains predominantly preclinical.
“Nevertheless, it is important to consider that the current evidence on MOTS-c remains predominantly preclinical”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [118]
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References 106 · Cited by 70
- Authors
- Wan, W., Zhang, L., Lin, Y., Rao, X., Wang, X., Hua, F., & Ying, J.
- Affiliations
- Second Affiliated Hospital of Nanchang University (CN)
- First Affiliated Hospital of Nanchang University (CN)
- Corresponding author
- Hua, Fuzhou
- Ying, Jun
- Venue
- Journal of Translational Medicine
- Published
- 2023-01-20
- Volume
- 21
- Issue
- 1
- Pages
- 36-36
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC9854231
- OpenAlex
- W4317569362
- Cited by
- 70
- References
- 106
- Citations by year
- 2026: 25 · 2025: 21 · 2024: 17 · 2023: 7
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82060219)
- Natural Science Foundation of Jiangxi Province (20212ACB216009, 20202BAB206033, 20212BAB216048)
- Jiangxi Province thousands of Plans (jxsq2019201023)
- Youth Team Project of the Second Affiliated Hospital of Nanchang University (2019YNTD12003)
- Postgraduate Innovation Special Foundation of Jiangxi Province (YC2022-S204)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- MOTS-c, mitochondrial peptides, 12S rRNA, retrograde signaling, AMPK, AICAR, energy metabolism, aging, insulin resistance, inflammation, physical activity, antioxidant response element, nuclear translocation
- MeSH terms
- Aging, Homeostasis, Humans, Insulin Resistance, Mitochondria, Peptides, Transcription Factors, Mitochondrial Proteins
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