Abstract
Although diabetes mellitus is known to be a disease associated with mitochondrial dysfunction, not everything is clear about mitochondrial Ca2+ transport and Ca2+-induced permeability transition in diabetic cells. The objective of this work was to study the operation of MCU and Ca2+-dependent mitochondrial permeabilization in the liver cells of Sprague-Dawley rats under the streptozotocin-induced type I diabetes. It was shown that two weeks after the induction of diabetes, the rate of Ca2+ uptake by the mitochondria of diabetic animals increased ~1.4-fold. The expression of MCU and MICU1 subunits did not change, yet the quantity of dominant-negative MCUb channel subunits was almost twice as lower. The organelles also became more resistant to the induction of CsA-sensitive MPT pore and less resistant to the induction of CsA-insensitive palmitate/Ca2+-induced pore. The mitochondria of diabetic liver cells also showed changes in the lipid matrix of their membranes. The content of fatty acids in the membranes grew, and microviscosity of the lipid bilayer (assessed with laurdan) increased. At the same time, lipid peroxidation (assessed by the production of malonic dialdehyde) was stimulated. The paper discusses the consequences of the diabetes-related changes in mitochondria in the context of cell physiology.
Highlights
Diabetes mellitus (DM) is one of the most common metabolic diseases which is associated with either impairment of insulin secretion or tolerance of cells to insulin
In addition to the cyclosporin A (CsA)-sensitive MPT pore, there was another variety of pores which could be opened in mitochondria in the presence of saturated fatty acids and Ca2+
Taking into account the fact that diabetes causes disorders in lipid metabolism, we have further investigated the formation of palmitate/Ca2+ -induced pore in liver mitochondria of diabetic animals
Summary
Diabetes mellitus (DM) is one of the most common metabolic diseases which is associated with either impairment of insulin secretion (type I diabetes) or tolerance of cells to insulin (type II diabetes). One of the main targets of diabetes are mitochondria. There are a lot of diabetes-related disorders, developing in the structure and function of mitochondria of various tissues and organs: Impairment of mitochondrial biogenesis, remodeling of the mitochondrial cell network, disorders in the system of oxidative phosphorylation, hyperproduction of reactive oxygen species, etc. One of the manifestations of mitochondrial dysfunction in diabetes mellitus are disorders in the mitochondrial Ca2+ ion transport systems. As a major buffer system of this ion, mitochondria are involved in the regulation of intracellular Ca2+ homeostasis and, in addition, Ca2+ activates a number of mitochondrial respiratory enzymes and enzymes of the Krebs cycle.
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