title: Cell biology. Metabolic control of cell death.
abstract: Beyond their contribution to basic metabolism, the major cellular organelles, in particular mitochondria, can determine whether cells respond to stress in an adaptive or suicidal manner. Thus, mitochondria can continuously adapt their shape to changing bioenergetic demands as they are subjected to quality control by autophagy, or they can undergo a lethal permeabilization process that initiates apoptosis. Along similar lines, multiple proteins involved in metabolic circuitries, including oxidative phosphorylation and transport of metabolites across membranes, may participate in the regulated or catastrophic dismantling of organelles. Many factors that were initially characterized as cell death regulators are now known to physically or functionally interact with metabolic enzymes. Thus, several metabolic cues regulate the propensity of cells to activate self-destructive programs, in part by acting on nutrient sensors. This suggests the existence of "metabolic checkpoints" that dictate cell fate in response to metabolic fluctuations. Here, we discuss recent insights into the intersection between metabolism and cell death regulation that have major implications for the comprehension and manipulation of unwarranted cell loss.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. douglas.green@stjude.org kroemer@orange.fr.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, F-75006 Paris, France. Université Paris Descartes/Paris V; Sorbonne Paris Cité; F-75005 Paris, France. INSERM, U1138, F-94805 Villejuif, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.affiliation: Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, F-75006 Paris, France. Université Paris Descartes/Paris V; Sorbonne Paris Cité; F-75005 Paris, France. INSERM, U1138, F-94805 Villejuif, France. Metabolomics and Cell Biology Platforms, Gustave Roussy, F-94805 Villejuif, France. Pôle de Biologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, F-75015 Paris, France. douglas.green@stjude.org kroemer@orange.fr.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D004734:Energy Metabolism; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D010539:Permeability; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D000105:Acetyl Coenzyme A; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases