Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver.

Autor: Henschke S; Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Nolte H; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Max Planck Institute for Biology of Ageing, Cologne, Germany., Magoley J; Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Kleele T; Institute of Physics, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland., Brandt C; Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Hausen AC; Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Wunderlich CM; Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Bauder CA; Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Aschauer P; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Manley S; Institute of Physics, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland., Langer T; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; Max Planck Institute for Biology of Ageing, Cologne, Germany., Wunderlich FT; Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Brüning JC; Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Cologne, Germany.; Policlinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University Hospital Cologne, Cologne, Germany.; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.; National Center for Diabetes Research (DZD), Neuherberg, Germany.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Apr 26; Vol. 384 (6694), pp. 438-446. Date of Electronic Publication: 2024 Apr 25.
DOI: 10.1126/science.adk1005
Abstrakt: 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.
Databáze: MEDLINE
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