Laboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia.
Int J Mol Sci. 2022 Nov 18;23(22):14327. doi: 10.3390/ijms232214327.
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.
这项工作研究了甲状腺素对大鼠肝线粒体生物发生和质量控制系统的影响。给实验动物长期服用甲状腺素会导致甲状腺功能亢进,这可以通过血清游离三碘甲状腺原氨酸和甲状腺素浓度增加几倍来证实。研究发现,随着 ADP 磷酸化效率和呼吸状态比的降低,耗氧量增加。电子显微镜显示,36%的肝线粒体肿胀,大约 18%的线粒体基质破裂,嵴数量减少。经常与有缺陷的线粒体相关的多层体位于细胞器的边缘或内部。患有甲状腺功能亢进症的大鼠线粒体的数量、面积和周长增加。甲状腺素的给药增加了肝组织中线粒体的生物发生和线粒体 DNA 的数量。线粒体动力学和线粒体自噬发生了显著变化。所得数据表明,过量的甲状腺激素会导致线粒体质量控制系统紊乱,并最终导致潜在毒性物质掺入线粒体库中。