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.
Keywords: ATP, calcium, ceramides, fatty acids, lipotoxicity, metabolic syndrome, mitochondria, reactive oxygen species
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