| First Author | Andersson S | Year | 2025 |
| Journal | Nat Metab | Volume | 7 |
| Issue | 7 | Pages | 1344-1357 |
| PubMed ID | 40659911 | Mgi Jnum | J:387709 |
| Mgi Id | MGI:8352905 | Doi | 10.1038/s42255-025-01325-7 |
| Citation | Andersson S, et al. (2025) Old mitochondria regulate niche renewal via alpha-ketoglutarate metabolism in stem cells. Nat Metab 7(7):1344-1357 |
| abstractText | Cellular metabolism is a key regulator of cell fate(1), raising the possibility that the recently discovered metabolic heterogeneity between newly synthesized and chronologically old organelles may affect stem cell fate in tissues(2,3). In the small intestine, intestinal stem cells (ISCs)(4) produce metabolically distinct progeny(5), including their Paneth cell (PC) niche(6). Here we show that asymmetric cell division of mouse ISCs generates a subset enriched for old mitochondria (ISC(mito-O)), which are metabolically distinct, and form organoids independently of niche because of their ability to recreate the PC niche. ISC(mito-O) mitochondria produce more alpha-ketoglutarate, driving ten-eleven translocation-mediated epigenetic changes that promote PC formation. In vivo alpha-ketoglutarate supplementation enhanced PC turnover and niche renewal, aiding recovery from chemotherapy-induced damage in aged mice. Our results reveal a subpopulation of ISCs whose old mitochondria metabolically regulate cell fate, and provide proof of principle for metabolically promoted replacement of specific aged cell types in vivo. |
