Exercise‐induced heart mitochondrial cholesterol depletion influences the inhibition of mitochondrial swelling

Abstract

New findings r What is the central question of this study?The central question was to establish whether decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and affect resistance to CaCl 2 -induced mitochondrial swelling. r What is the main finding and its importance?The main finding is the indication that changes in the cholesterol pool in heart mitochondria induced by swimming exercise are related to an increase in resistance to CaCl 2 -induced swelling, probably by remodelling of lipid microdomains, and are not deleterious for mitochondrial bioenergetics. These findings may contribute to a more complete understanding of the defense system that may prevent mitochondrial degradation during exercise and the protective system of cardiac cell defense in stress conditions. The significance of the reduction of the cholesterol pool in heart mitochondria after exercise is still unknown. Recently, published data have suggested that cholesterol may influence the components of mitochondrial contact site and affect mitochondrial swelling. Therefore, the aim of this study was to determine whether the decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling. Male Wistar rats were divided into a sedentary control group and an exercise group. The rats exercised for 3 h, burdened with an additional 3% of their body weight. Their hearts were removed immediately after completing the exercise. The left ventricle was divided and used for experiments. Mitochondrial cholesterol content, membrane fluidity and mitochondrial bioenergetics were measured in the control and exercised rat heart mitochondria. To assess whether mitochondrial modifications are linked to disruption of lipid microdomains, methyl-β-cyclodextrin, a well-known lipid microdomain-disrupting agent and cholesterol chelator, was applied to the mitochondria of the control group. Cholesterol depletion, increased membrane fluidity and increased resistance to calcium chloride-induced swelling were observed in postexercise heart crude mitochondrial fraction. Similar results were achieved in control mitochondria treated with 2% methyl-β-cyclodextrin. All of the mitochondrial bioenergetics parameters were similar between the groups.

Interaction of Mitochondria with the Endoplasmic Reticulum and Plasma Membrane in Calcium Homeostasis, Lipid Trafficking and Mitochondrial Structure

“…Why the free cholesterol content of purified MAM is 7 times higher than that of microsomes still remains unclear [ 3 ]. Cholesterol depletion in MAM induced by methyl- -cyclodextrin significantly increases the association of mitochondria with the ER [ 3 ] and influences mitochondrial bioenergetics and structure [ 145 , 146 ]. Moreover, in the spinal cords of ALS patients and in a transgenic mouse model of ALS (Cu/Zn SOD mice), levels of sphingomyelin, ceramides and cholesteryl esters were significantly increased, indicating the possibility of MAM disequilibrium [ 147 ].…”

Exercise‐Induced Changes in Caveolin‐1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver

“…The rats were prepared for the experiments and exercise tests using the previously described methods [ 2 , 16 ]. The rats were randomly divided into sedentary controls (C) and long-lasting endurance exercise (E) groups.…”

“…Therefore, the aim of this study was to investigate the effect of prolonged swimming on mitochondrial Cav-1 and cholesterol concentrations as well as the induction of changes in mitochondrial swelling in rat skeletal muscles and livers. Based on our previous data [ 2 ], we hypothesize that both exercise-induced changes in the mitochondrial swelling and mitochondrial cholesterol levels will occur with concomitant increases in Cav-1 concentrations in the skeletal muscle mitochondria but not in the liver.…”

“…The reduction in cholesterol in rat heart mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling; however, this change does not influence the mitochondrial bioenergetics and oxidative stress. [ 1 , 2 ]. It has been proposed that this phenomenon may be involved in the protection mechanism of mitochondria during exercise or during other stressful conditions [ 2 ].…”

“…[ 1 , 2 ]. It has been proposed that this phenomenon may be involved in the protection mechanism of mitochondria during exercise or during other stressful conditions [ 2 ].…”