title: Mitochondrial dysfunction and lipid homeostasis.
abstract: This review is aimed at illustrating that mitochondrial dysfunction and altered lipid homeostasis may concur in a variety of pathogenesis states, being either contributive or consecutive to primary disease events. Underlying mechanisms for this concurrence are far from being the exhaustive elements taking place in disease development. They may however complicate, contribute or cause the disease. In the first part of the review, physiological roles of mitochondria in coordinating lipid metabolism and in controlling reactive oxygen species (ROS), ATP and calcium levels are briefly presented. In a second part, clues for how mitochondria-driven alterations in lipid metabolism may induce toxicity are discussed. In the third part, it is illustrated how mitochondrial dysfunction and lipid homeostasis disruption may be associated (i) to complicate type 1 diabetes (pancreatic β-cell mitochondrial dysfunction in ATP yield induces reduced insulin secretion and hence disruption of glucose and lipid metabolism), (ii) to contribute to type 2 diabetes and other insulin resistant states (mitochondrial impairment may induce adipocyte dysfunction with subsequent increase in circulating free fatty acids and their abnormal deposit in non adipose tissues (pancreatic β-cells, skeletal muscle and liver) which results in lipotoxicity and mitochondrial dysfunction), (iii) to offer new clues in our understanding of how the brain controls feeding supply and energy expenditure, (iv) to promote cancer development notably via fatty acid oxidation/synthesis imbalance (in favor of synthesis) further strengthened in some cancers by a lipogenetic benefit induced by a HER2/fatty acid synthase cross-talk, and (v) to favor cardiovascular disorders by impacting heart function and arterial wall integrity.
authors.affiliation: Inserm Lab Ext, CHRU Lille, 59037 Lille, France. joseph.vamecq@inserm.fr
authors.forename: Joseph
authors.initials: J
authors.lastname: Vamecq
authors.forename: Anne-Frederique
authors.initials: AF
authors.lastname: Dessein
authors.forename: Monique
authors.initials: M
authors.lastname: Fontaine
authors.forename: Gilbert
authors.initials: G
authors.lastname: Briand
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.forename: Norbert
authors.initials: N
authors.lastname: Latruffe
authors.forename: Pierre
authors.initials: P
authors.lastname: Andreolotti
authors.forename: Mustapha
authors.initials: M
authors.lastname: Cherkaoui-Malki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D002118:Calcium