CRITICAL FUNCTIONS OF MITOCHONDRIA IN THE ONSET OF PATHOLOGIES

Original title

КРИТИЧЕСКИЕ ФУНКЦИИ МИТОХОНДРИЙ В ВОЗНИКНОВЕНИИ ПАТОЛОГИЙ

Authors

D. B. Zorov¹, E. Y. Plotnikov¹, D. N. Silachev1, L. D. Zorova1, I. B. Pevzner¹, V. A. Babenko¹, V. A. Popkov^{1, 2}, S. D. Zorov², N. V.

Contact information

¹A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, e-mail Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра.

²Faculty of Bioinformatics and Bioengineering, Moscow State University, Moscow

Pages

41-43

DOI

10.31255/978-5-94797-318-1-41-43

Abstract

It has become proven a fact that mitochondria are responsible for many pathologies most of them not related with energy production. To correctly perform functioning of mitochondria, they need to proceed the mechanism of mitochondrial quality control which utilizes malfunctional mitochondria. The key role in this mechanism is played by the transmembrane potential (Δψ) on the inner mitochondrial membrane. Mitochondria unable to maintain the optimal value of Δψ are disposed via mitophagy. This requirement is particularly clear under hypoxic conditions, when the mitochondria are unable to perform the oxidative synthesis of ATP, but instead, use intracellular ATP to maintain Δψ due to the reversal of the operation of ATP synthase. Note that this is happening under conditions of energy crisis, when the entire cell is experiencing serious problems due to imbalance between production and consumption of ATP. One of the serious causes of pathologies including aging is the violation of these links, which leads to that even mitochondria with non-optimal values of Δψ are not utilized in the cell resulting in an increase in the heterogeneity of the mitochondrial population in the cell. We suggest that the heterogeneity of Δψ in the cell is the primary cause of pathologies and aging. The basis for the creation of a heterogeneous mitochondrial population is the process of mitochondrial fragmentation (fission) as a response to damage to mitochondria. In this case, an intramitochondrial restructuring occurs leading to separation of damaged from intact parts of the mitochondrion. The subsequent asymmetric division of mitochondria leads to the formation of intact mitochondria, which subsequently form a fully functioning mitochondrial reticulum in the cell, while damaged, poorly functioning mitochondrial fragments undergo the process of digestion (mitophagy). The process of mitophagy starts with the tagging of damaged mitochondria, followed by the formation of an autophagosome, which subsequently merges with the lysosome, resulting in complete degradation of damaged mitochondria. Such permanent destruction of damaged and unwanted mitochondria is a prerequisite for the normal functioning of cells and ideally there is a balance within a cell between the formation of new and the destruction of old mitochondria. However, under real conditions, there is a deviation from the ideal picture, and damaged mitochondria are passed through the selective filter, either due to the corruption of the machinery tagging damaged mitochondria, or due to damage to the mechanism of mitophagy. Any of these causes will eventually lead to heterogeneity of the mitochondrial population, as the driving force of pathologies and aging.

Supported by the Russian Science Foundation (grant 14-15-00147)