MOTS-c & Mitochondrial Peptides in Health & Aging | David Lee | Episode 302

Send us Fan Mail Mitochondrial peptide MOTS-c is a stress-induced signal that reprograms cell metabolism. **TOPICS DISCUSSED:** - **Mitochondrial Roles:** Not just ATP production, but “speaker of the house” via communication molecules that “talk” to the rest of the cell. - **Origin of Communication:** Mitochondrial peptides were likely co-opted from ancient antimicrobial factors to synchronize nuclear and mitochondrial genomes. - **MOTC Discovery:** Identified in mitochondrial ribosomal RNA regions linked to interferon responses. - **Stress Induction:** MOTS-c is produced in response to exercise, immune activation, and nutrient withdrawal; circulates as a mitokine. - **Nuclear Regulation:** MOTS-c translocates to the nucleus under stress and acts as a nonspecific cofactor that shapes chromatin accessibility and gene expression. - **Metabolic Effects:** Prevents diet-induced obesity and fatty liver in mice without altering baseline weight; engages AMPK and suppresses anabolic pathways. - **Immune Modulation:** Shifts immune cell programs to reduce autoimmune attack in type 1 diabetes models. - **Aging Phenotypes:** Daily or intermittent dosing doubles running capacity and preserves walking ability in old mice. **ABOUT THE GUEST:** Changhan David Lee, PhD is Associate Professor at the University of Southern California Leonard Davis School of Gerontology. His laboratory investigates mitochondrial communication and microproteins in the biology of aging.  **RELATED CONTENT:** - Article | MOTS-c & Cellular Energy Homeostasis Support the show **Support my work:** - Good Chemistry: Personalized, science-based health consulting. Work with Dr. Nick Jikomes directly. - Affiliate Partners: Visit this link to see my affiliate partners and get discounts codes for products & services to support health. For all the ways you can support my efforts.