Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver

• 成果类型: Article
• 署名作者: Henschke, Sinika; Nolte, Hendrik; Magoley, Judith; Kleele, Tatjana; Brandt, Claus; Hausen, A. Christine; Wunderlich, Claudia M.; Bauder, Corinna A.; Aschauer, Philipp; Manley, Suliana; Langer, Thomas; Wunderlich, F. Thomas; Bruening, Jens C.
• 署名单位: University of Cologne; University of Cologne; University of Cologne; Max Planck Society; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Graz; German Center for Diabetes Research (DZD)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9397
• DOI: 10.1126/science.adk1005
• 发表日期: 2024-04-26
• 页码: 438-446
• 关键词: insulin sensitivity; mitofusin 2; glucose; neurons; fission; image; DYNAMICS; mff; identification; homeostasis

摘要

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 MFFS131G knock-in mutation abrogated AKT-induced mitochondrial fragmentation in vitro. In vivo, MFFS131G 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.