[Back to Issue 10 ToC] [Back to Journal Contents] [Back to Biochemistry (Moscow) Home page]
[View Full Article] [Download Reprint (PDF)]

REVIEW: Decrease in ATP Biosynthesis and Dysfunction of Biological Membranes. Two Possible Key Mechanisms of Phenoptosis

A. V. Rzheshevsky

Center for Rehabilitation Medicine, ul. Mechnikova 8, 49000 Dnepropetrovsk, Ukraine; E-mail: alex-rjechewsky@mail.ru

Received April 11, 2014; Revision received May 12, 2014
Metabolic syndrome is extremely prevalent in the world and can be considered as one of main factors leading to accelerated aging and premature death. This syndrome may be closely linked with age-related disruptions in hypothalamic–pituitary system function, which perhaps represent a trigger mechanism of development of endocrine and cardiovascular pathologies. Age-related elevation of the sensitivity threshold of the hypothalamus to regulatory signals in association with low mobility and excessive diet trigger a cascade of biochemical reactions that might be used for activation of programmed death of the organism – phenoptosis. Accumulation of fatty acids in a cell and resulting lipotoxicity include resistance to insulin and leptin, endoplasmic reticulum stress, uncoupling of oxidation and phosphorylation, and dysfunction of biological membranes. Decrease in ATP synthesis is correlated with accumulation of calcium ions in cells, dysfunction of mitochondria, and increasing apoptotic activity. Age-related activation of mTOR (which is greatly influenced by excess energy substrates) has deleterious impact on one of the main mechanisms of cell defense by which defective mitochondria are replaced: mitophagy and biogenesis of mitochondria will be suppressed, and this will increase in greater degree mitochondrial dysfunction and oxidative stress. Fatty acid-induced inflammation will increase activity of nuclear factor NF-κB, the well-known stimulator of age-related pathologies. The final stage of phenoptosis can be represented by endothelium dysfunction related with oxidative stress, insulin resistance, and the most prevalent cardiovascular pathologies.
KEY WORDS: fatty acids, leptin, insulin, AMP-activated protein kinase, mTOR, oxidative stress, apoptosis, phenoptosis, biomembranes dysfunction, mitochondria, endoplasmic reticulum

DOI: 10.1134/S0006297914100071