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

Wiesław Ziółkowski , Dhivya Vadhana , Jan Kaczor , Robert Olek , Damian Flis , Małgorzata Hałoń , Michal Woźniak , Donatella Fedeli , Manuel Carloni , Jędrzej Antosiewicz , Rosita Gabbianelli

Abstract

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 affectmitochondrial swelling. Therefore, the aim of this study was to determine whether the decreased cholesterol content in heartmitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling.MaleWistar 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 themitochondrial bioenergetics parameterswere similar between the groups.