Transport of Ca2+ and Ca2+-Dependent Permeability Transition in the Liver and Heart Mitochondria of Rats with Different Tolerance to Acute Hypoxia.

Konstantin Belosludtsev,Vlada Starinets,Mikhail Dubinin,Kirill Tenkov,Natalia Belosludtseva,Eugeny Talanov,Nadezhda Zakharova

doi:10.3390/biom10010114

Konstantin Belosludtsev, Vlada Starinets + Show 5 more

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https://doi.org/10.3390/biom10010114

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Abstract

The work examines the kinetic parameters of Ca2+ uptake via the mitochondrial calcium uniporter complex (MCUC) and the opening of the Ca2+-dependent permeability transition pore (MPT pore) in the liver and heart mitochondria of rats with high resistance (HR) and low resistance (LR) to acute hypoxia. We found that the rate of Ca2+ uptake by mitochondria of the liver and heart in HR rats is higher than that in LR rats, which is associated with a higher level of the channel-forming subunit MCU in liver mitochondria of HR rats and a lower content of the dominant-negative channel subunit MCUb in heart mitochondria of HR rats. It was shown that the liver mitochondria of HR rats are more resistant to the induction of the MPT pore than those of LR rats (the calcium retention capacity of liver mitochondria of HR rats was found to be 1.3 times greater than that of LR rats). These data correlate with the fact that the level of F0F1-ATP synthase, a possible structural element of the MPT pore, in the liver mitochondria of HR rats is lower than in LR rats. In heart mitochondria of rats of the two phenotypes, no statistically significant difference in the formation of the MPT pore was revealed. The paper discusses how changes in the expression of the MCUC subunits and the putative components of the MPT pore can affect Ca2+ homeostasis of mitochondria in animals with originally different tolerance to hypoxia and in hypoxia-induced tissue injury.

Highlights

Hypoxia/ischemia is a widespread phenomenon that occurs both in conditions of oxygen deficiency in the environment and in various pathologies as a result of a decrease in oxygen delivery to the cell to a level insufficient to maintain its functions and structure
One can see that the rate of Ca2+ influx into the liver mitochondria of high resistance (HR) rats is 1.3 times higher compared with that of low resistance (LR) rats (Figure 1B)
Our results indicate that the levels of cyclophilin D and ANT1 in mitochondria of the liver of HR and LR rats are not distinguished

Summary

Introduction

Hypoxia/ischemia is a widespread phenomenon that occurs both in conditions of oxygen deficiency in the environment and in various pathologies as a result of a decrease in oxygen delivery to the cell to a level insufficient to maintain its functions and structure. The main intracellular targets of hypoxia of various etiologies are mitochondria and aerobic energy metabolism [1,2]. Excessive accumulation of Ca2+ in cytoplasm and mitochondria in hypoxia and subsequent reoxygenation can initiate cell injury and death via the opening of the Ca2+-dependent mitochondrial permeability transition pore (MPT pore) and the subsequent release of proapoptotic proteins from organelles [3]. Changes in mitochondrial [Ca2+] modulate key cellular processes, ranging from aerobic metabolism (through Ca2+-sensitive dehydrogenases, and enzymes of the Krebs cycle [4]) to the release of proapoptotic factors [5,6,7,8], as well as local modulation of the activity of channels and enzymes [9,10]

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