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

Cells. 2023 Jan 21;12(3):396. doi: 10.3390/cells12030396.

Abstract

This work investigated the effect of thyroxine on the biogenesis and quality control system in rat heart mitochondria. In hyperthyroid rats, the concentrations of free triiodothyronine and thyroxine increased severalfold, indicating the development of hyperthyroidism in these animals. The electron microscopy showed 58% of cardiac mitochondria to be in a swollen state. Some organelles were damaged and had a reduced number of cristae. Multilamellar bodies formed from cristae/membranes were found in the vacuolated part of the mitochondria. The hyperthyroidism caused no changes to mitochondrial biogenesis in the investigated animals. At the same time, the levels of mitochondrial dynamics proteins OPA1 and Drp1 increased in the hyperthyroid rats. The administration of thyroxine to the animals led to a decrease in the amount of PINK1 and Parkin in heart tissue. The data suggest that excess thyroid hormones lead to changes in mitochondrial dynamics and impair Parkin-dependent mitophagy in hyperthyroid rat heart.

Keywords: energy metabolism; mitochondrial dysfunction; mitophagy; quality control system; thyroid hormones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hyperthyroidism* / metabolism
  • Mitochondria, Heart / metabolism
  • Mitochondrial Proteins / metabolism
  • Mitophagy*
  • Rats
  • Thyroxine / pharmacology
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Mitochondrial Proteins
  • Thyroxine
  • Ubiquitin-Protein Ligases
  • PTEN-induced putative kinase
  • parkin protein

Grants and funding

This study was funded by grants from the Russian Foundation for Basic Research (RFBR) (project No. 20-015-00132 A to Natalia Venediktova).