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.

Dibenzylideneacetones Are Potent Trypanocidal Compounds That Affect the Trypanosoma cruzi Redox System

“…Mitochondrial dysfunction may lead to an increase in ROS/RNS; conversely, an increase in ROS/RNS may induce mitochondrial dysfunction (56). Based on our results, our hypothesis is that the mechanism of action of A3K2A1 and A3K2A3 involves an increase in ROS/RNS production, followed by mitochondrial depolarization.…”

Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21

“…Accumulating evidence supports important relationships between mitochondrial and immune function suggesting that impaired mitochondrial health associates with greater inflammation (Hahn, et al 2014; Qatanani, et al 2013; Vamecq, et al 2012)). Whereas lean adipose tissue is characterized by the absence of inflammation and increased mitochondrial function (Flachs, et al 2013), obese/sedentary adipose tissue is typified by a pro-inflammatory phenotype and impaired mitochondrial activity (Okamoto, et al 2007).…”

Cardiomyocyte-specific Loss of Diacylglycerol Acyltransferase 1 (DGAT1) Reproduces the Abnormalities in Lipids Found in Severe Heart Failure

“…How do these changes in lipid metabolism alter heart function? Many pathways are likely to be activated in the setting of lipotoxicity including those leading to formation of excess reactive oxygen (44), creation of endoplasmic reticulum stress (45), development of apoptosis (45,46), and dysfunction of mitochondria (44). Previous data from our laboratory and others have implicated excess PKC activation as causing heart toxicity (47,48).…”