Structural and Dynamic Features of Liver Mitochondria and Mitophagy in Rats with Hyperthyroidism

Abstract

This work investigated the effect of thyroxine on the biogenesis and quality control system of rat liver mitochondria. Chronic administration of thyroxine to experimental animals induced hyperthyroidism, which was confirmed by a severalfold increase in serum-free triiodothyronine and thyroxine concentrations. The uptake of oxygen was found to increase with a decrease in ADP phosphorylation efficiency and respiratory state ratio. Electron microscopy showed 36% of liver mitochondria to be swollen and approximately 18% to have a lysed matrix with a reduced number of cristae. Frequently encountered multilamellar bodies associated with defective mitochondria were located either at the edge of or inside the organelle. The number, area and perimeter of hyperthyroid rat mitochondria increased. Administration of thyroxine increased mitochondrial biogenesis and the quantity of mitochondrial DNA in liver tissue. Mitochondrial dynamics and mitophagy changed significantly. The data obtained indicate that excess thyroid hormones cause a disturbance of the mitochondrial quality control system and ultimately to the incorporation of potentially toxic material in the mitochondrial pool.

Effect of Thyroxine on the Structural and Dynamic Features of Cardiac Mitochondria and Mitophagy in Rats

“…It is the liver, unlike other organs, that is exposed to the strongest effects of the investigated substances during intraperitoneal administration. Thus, the results after the introduction of TH are likely to differ in the investigated animal organs, depending on the individual characteristics of the animal [12].…”

“…Samples of the heart tissue for the transmission electron microscopy (TEM) imaging were taken from decapitated animals and fixed in a 2.5% glutaraldehyde solution in 0.1 M phosphate-buffered saline (PBS, pH 7.4) for 2-3 h [12]. The preparations were examined and photographed using a JEM-2000 FXII (JEOL Ltd., Tokyo, Japan).…”

“…The concentration of the protein was determined by the Lowry method [15]. The samples (30-50 µg) were diluted in Laemmli buffer, separated by 12.5% SDS-PAGE, and transferred to a nitrocellulose membrane (Thermo Fisher Scientific, Wilmington, USA) [12]. The relative levels of the detected proteins were visualized using a C-DiGit Blot Scanner (LI-COR Biotechnology, Lincoln, Nebraska, USA) and normalized to the appropriate loading control.…”

"Ultrastructure of the Mitochondrial Membrane and Respiratory Ensembles"

“…Radin, Muller and their collaborators have recently shown that stable two-layered lipid structures, resembling in their physical properties the lipid layers of natural membranes, can be reconstructed from crude extracts of brain lipids. A drop of brain lipid solution in a chloroform-methanol mixture [42] was placed in a narrow slit in a plastic partition between chambers containing a solution of KS1. As the solvents diffuse from the droplet into the aqueous phase, the oriented phospholipid molecules at the boundary of the two solvents in the droplet approach each other and eventually combine into a fairly stable double layer located across the gap.…”

Effects of the Long-Term Administration of Uridine on the Functioning of Rat Liver Mitochondria in Hyperthyroidism

“…In this case, marked functional and structural changes occur in mitochondria. It is known that mitochondrial dysfunction plays an important role in both the development and progression of HT, especially due to the generation of oxidative stress, impaired oxidative phosphorylation, and improper operation of the system of mitochondrial quality control and mitophagy [4][5][6].…”