PMID-29983246 – MOTS-c Translocates to Nucleus to Regulate Gene Expression
Kim KH, Son JM, Benayoun BA, Lee C. "The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress," Cell Metabolism, 2018;28(3):516-524.e7. doi:10.1016/j.cmet.2018.06.008
Quick Reference
| Property | Value |
|---|---|
| PMID | 29983246 |
| DOI | 10.1016/j.cmet.2018.06.008 |
| Year | 2018 |
| Journal | Cell Metabolism |
| Study Type | In vitro / Mechanistic |
| Evidence Level | V |
| Sample | Cell-based experiments (HEK293, myocytes) |
| Peptide(s) Studied | MOTS-C |
Key Findings
- MOTS-c undergoes AMPK-dependent nuclear translocation under metabolic stress
- In the nucleus, MOTS-c interacts with ARE/ETS transcription factor motifs
- Regulates adaptive nuclear gene expression in response to glucose restriction, oxidative stress, and serum deprivation
- Establishes a novel mitochondria-to-nucleus retrograde signaling paradigm
- First demonstration that a mitochondrial-encoded peptide directly regulates nuclear gene expression
Study Design
Cell-based mechanistic study. Used HEK293 cells and myocytes with various metabolic stressors. Immunofluorescence for nuclear translocation. ChIP-seq for chromatin binding. AMPK inhibition experiments for pathway dependency.
Limitations
- In vitro only; nuclear translocation not confirmed in vivo
- Cell line models may not reflect muscle tissue physiology
- Single concentration/timepoint analyses
Clinical Relevance
Foundational mechanistic paper from the Lee lab, published in Cell Metabolism (IF ~29). Establishes that MOTS-c is not merely a circulating peptide but actively enters the nucleus to modulate gene expression — a paradigm-shifting finding for mitochondrial biology. Provides the molecular mechanism underlying MOTS-c's exercise mimetic and metabolic effects.
Related
#research #in-vitro #evidence-level-V