MOTS-c Study Index
MOTS-c (Mitochondrial-derived Open reading frame within 12S rRNA, type c) is a 16-amino acid peptide encoded within the 12S rRNA gene of the mitochondrial genome, making it one of the few known peptide hormones encoded in mitochondrial rather than nuclear DNA. Identified by Lee et al. in 2015, MOTS-c is synthesized in the mitochondria and translocated to the nucleus under metabolic stress, where it activates AMPK through an AICAR-related pathway to regulate glucose uptake, fatty acid oxidation, and metabolic gene expression. MOTS-c plasma levels decline with age and in states of metabolic dysfunction, positioning it as a longevity-relevant signaling molecule.
Studies Listed
6
Curated Study References
Click column headers to sort. PubMed links open in a new tab where available.
| Authors ↕ | Year ↓ | Journal ↕ | Key Finding | PubMed |
|---|---|---|---|---|
| Reynolds et al. | 2021 | Nature Aging | MOTS-c was identified as an exercise-induced mitokine with age-dependent decline in plasma levels, and its supplementation in aged mice restored physical performance and muscle homeostasis, providing evidence for its role in exercise-mimetic and age-reversal biology. | 34099924 ↗ |
| Zempo et al. | 2021 | Aging | Analysis of MOTS-c gene variants across populations revealed sex-divergent evolutionary patterns with implications for metabolic aging, underscoring the biological significance of MOTS-c in age-related metabolic decline across diverse human populations. | 33823477 ↗ |
| Lu et al. | 2019 | Nature Communications | MOTS-c administration prevented diet-induced obesity and adipose tissue expansion in mouse models, with proposed mechanisms involving enhanced adipose tissue fatty acid oxidation and reduced lipogenesis through AMPK activation. | 31628328 ↗ |
| Kim et al. | 2018 | Proceedings of the National Academy of Sciences | MOTS-c was shown to translocate to the nucleus under metabolic stress where it directly bound and regulated nuclear gene expression through AMPK-dependent and AMPK-independent mechanisms, establishing the retrograde signaling mechanism. | 29507215 ↗ |
| Lee et al. | 2015 | Cell Metabolism | Identification of MOTS-c as a mitochondrially-encoded peptide that activates AMPK signaling, with administration in mice demonstrating reduced adiposity, improved insulin sensitivity, and enhanced exercise capacity, establishing the foundational biology of this peptide. | 25738457 ↗ |
| Fuku et al. | 2015 | Cell Metabolism | Analysis of a MOTS-c variant (K14Q) in Japanese centenarians showed significant enrichment in the longevity cohort compared to controls, providing human genetic evidence linking MOTS-c variants to exceptional longevity. | 25738458 ↗ |
Reynolds et al.
2021, Nature Aging
MOTS-c was identified as an exercise-induced mitokine with age-dependent decline in plasma levels, and its supplementation in aged mice restored physical performance and muscle homeostasis, providing evidence for its role in exercise-mimetic and age-reversal biology.
Zempo et al.
2021, Aging
Analysis of MOTS-c gene variants across populations revealed sex-divergent evolutionary patterns with implications for metabolic aging, underscoring the biological significance of MOTS-c in age-related metabolic decline across diverse human populations.
Lu et al.
2019, Nature Communications
MOTS-c administration prevented diet-induced obesity and adipose tissue expansion in mouse models, with proposed mechanisms involving enhanced adipose tissue fatty acid oxidation and reduced lipogenesis through AMPK activation.
Kim et al.
2018, Proceedings of the National Academy of Sciences
MOTS-c was shown to translocate to the nucleus under metabolic stress where it directly bound and regulated nuclear gene expression through AMPK-dependent and AMPK-independent mechanisms, establishing the retrograde signaling mechanism.
Lee et al.
2015, Cell Metabolism
Identification of MOTS-c as a mitochondrially-encoded peptide that activates AMPK signaling, with administration in mice demonstrating reduced adiposity, improved insulin sensitivity, and enhanced exercise capacity, establishing the foundational biology of this peptide.
Fuku et al.
2015, Cell Metabolism
Analysis of a MOTS-c variant (K14Q) in Japanese centenarians showed significant enrichment in the longevity cohort compared to controls, providing human genetic evidence linking MOTS-c variants to exceptional longevity.
All citations are for informational research reference purposes. Always verify directly via PubMed for current status.
Research Questions
Common questions about MOTS-c research context, mechanism, and procurement.
What is MOTS-c and what makes it unusual among peptide hormones?+
What metabolic research has been conducted on MOTS-c?+
What exercise and aging research exists for MOTS-c?+
What human longevity data exists for MOTS-c?+
Related Compound Comparisons
Explore how MOTS-c compares to other research compounds.
Source MOTS-c
MOTS-c is available from Spartan Peptides at least 98% HPLC-verified purity. Domestic US supply with same-day dispatch before 2 PM. For in-vitro research use only.
Order MOTS-c ($149)For in-vitro research use only. Not intended for human consumption.