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. 2025 Nov 27;14(23):1877.
doi: 10.3390/cells14231877.

Imbalance in MICOS Proteins in Rat Liver Mitochondria in an Induced Hyperthyroidism Model

Natalya Venediktova  1 , Ilya Solomadin  1 , Anna Nikiforova  1 , Tatiana Bessonova  2   3
Affiliations

Imbalance in MICOS Proteins in Rat Liver Mitochondria in an Induced Hyperthyroidism Model

Natalya Venediktova et al. Cells. .

Abstract

This study investigated rearrangements in the cristae structure and the possible relationship between these changes and the MICOS levels in the liver mitochondria of rats with experimentally induced hyperthyroidism. In hyperthyroid rats (HRs), the number, area, and perimeter of mitochondria were increased, and organelles of a worm-shaped, branched, highly elongated, or spherical shape appeared. A structural change in the mitochondria of HR liver was detected, consisting of a decrease in the number of cristae relative to the cross-section of the organelle. In some mitochondria, multilamellar bodies were detected. Hyperthyroidism caused an increase in the expression of genes and the level of proteins of the MIC60 subcomplex, with an unchanged level of the MIC10 subcomplex. Moreover, the levels of Sam50 and OPA1 in HRs were reduced. A functional assessment of HR mitochondria revealed changes in oxygen consumption, a decrease in membrane potential, and disruption of Ca2+ homeostasis. These data indicate that excess thyroid hormones cause partial changes in liver mitochondrial structure and an imbalance in the levels of Mic60 and Mic10 subcomplex proteins. The decreased levels of Sam50 and OPA1 proteins suggest their potential as targets for correcting mitochondrial dysfunction in metabolic disorders.

Keywords: MICOS; OPA1; calcium retention capacity; cardiolipin; cristae membranes; hyperthyroidism; oxidative phosphorylation.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Effect of T4 on the baseline expression of the MICOS and taffazin genes in rat liver. A heat map displays fold change in gene expression in hyperthyroid rats compared to control rats. Fold change (2−ΔΔCt) is the normalized gene expression (2−ΔCt) in the HT group divided the normalized gene expression (2−ΔCt) in the control group. C, control rats; HT, hyperthyroid rats, n = 6–7 for C, n = 7 for HT.
Figure 2
Figure 2
Western blot of Mic27, Mic13, Mic10, ATP5E and VDAC; C1–C5, control rats; HT1–HT5, hyperthyroid rats. Relative levels of appropriate proteins to VDAC (n = 5 in each group).
Figure 3
Figure 3
Western blot of Mic60, Mic25, Mic19, Sam50, OPA1 and VDAC; C1–C5, control rats; HT1–HT5, hyperthyroid rats. Relative levels of appropriate proteins to VDAC. * p < 0.05; ** p < 0.02 as compared with the control data (n = 5 in each group).
Figure 4
Figure 4
TEM images of hepatic tissue in the control (A–A2) and in experimental hyperthyroidism (B–B3). The insets in (B) represent examples of mitochondria found in hepatocytes of hyperthyroid rats. The number of examined images in each group was about 40. Black asterisks, multilamellar bodies; yellow asterisks, swollen mitochondria; red asterisks, damaged mitochondria; EC and red arrows, expanded mitochondrial cristae.
Figure 5
Figure 5
Western blot of NRF1, TFAM and GAPDH; C1–C5, control rats; HT1–HT5, hyperthyroid rats. Relative levels of appropriate proteins to GAPDH. ** p < 0.02 as compared with the control data (n = 5 in each group).
Figure 6
Figure 6
Calcium retention capacity (A), membrane potential (B) and cardiolipin level (C) in isolated liver mitochondria of control and hyperthyroid rats. C, control rats; HT, hyperthyroid rats. * p < 0.05 as compared with the control data (n = 5 in each group).
Figure 7
Figure 7
Components of mitochondrial cristae in normal conditions (1) and in HT (2).
See this image and copyright information in PMC

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