Operation of the Permeability Transition Pore in Rat Heart Mitochondria in Aging

Abstract

The functioning of the mitochondrial permeability transition pore (mPTP) is involved in the mechanism of programmed cell death and mitochondrial dysfunction observed with aging. In this work, the functional state of heart mitochondria isolated from young (mature and 2–3-month-old) and old (20–22-month-old) rats under conditions of mPTP opening was studied. In the mitochondria of old rats, the rates of Ca²⁺ and TPP⁺ absorption decreased by 40 and 42%, respectively, the threshold concentration of Ca²⁺ decreased by 20%, and the swelling rate of mitochondria from old animals was by 40% higher than that of mitochondria from young ones. In the heart mitochondria of old animals, the content and production of reactive oxygen species (ROS) varied, the superoxide anion content was increased, and the level of hydroperoxide (H₂O₂) increased at a threshold calcium concentration. Electron microscopy revealed a decrease in the number of cristae in mitochondria of the rat heart during aging. To study the potential role of proteins modulating the mPTP functioning, the content of 2',3'-cyclonucleotide-3'-phosphodiesterase (CNPase) and translocator protein (TSPO) in the heart mitochondria of rats of different ages was measured. A significant age-related decrease in the level of CNPase and an increase in the amount of TSPO were detected. The role of these proteins in mitochondrial dysfunction observed during aging is discussed.