| First Author | Henschke S | Year | 2024 |
| Journal | Science | Volume | 384 |
| Issue | 6694 | Pages | 438-446 |
| PubMed ID | 38662831 | Mgi Jnum | J:362859 |
| Mgi Id | MGI:7643263 | Doi | 10.1126/science.adk1005 |
| Citation | Henschke S, et al. (2024) Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver. Science 384(6694):438-446 |
| abstractText | Liver mitochondria play a central role in metabolic adaptations to changing nutritional states, yet their dynamic regulation upon anticipated changes in nutrient availability has remained unaddressed. Here, we found that sensory food perception rapidly induced mitochondrial fragmentation in the liver through protein kinase B/AKT (AKT)-dependent phosphorylation of serine 131 of the mitochondrial fission factor (MFFS131). This response was mediated by activation of hypothalamic pro-opiomelanocortin (POMC)-expressing neurons. A nonphosphorylatable MFF(S131G) knock-in mutation abrogated AKT-induced mitochondrial fragmentation in vitro. In vivo, MFF(S131G) knock-in mice displayed altered liver mitochondrial dynamics and impaired insulin-stimulated suppression of hepatic glucose production. Thus, rapid activation of a hypothalamus-liver axis can adapt mitochondrial function to anticipated changes of nutritional state in control of hepatic glucose metabolism. |
