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Cardiolipin-dependent decrease of cytochrome c oxidase activity in heart mitochondria from hypothyroid rats
G Paradies1, G Petrosillo, F M Ruggiero
1Department of Biochemistry and Molecular Biology, University of Bari, Italy.
Insights
Thyroid hormone deficiency reduces heart mitochondrial cytochrome oxidase activity. Supplementing with cardiolipin (a key mitochondrial phospholipid) fully restored this enzyme activity, confirming cardiolipin's crucial role.
Area of Science:
- Biochemistry
- Mitochondrial Biology
- Endocrinology
Background:
- Cardiolipin is essential for mitochondrial membrane structure and function.
- Previous studies indicated reduced cytochrome c oxidase activity in hypothyroid rat hearts.
- A potential role for cardiolipin in this reduction was hypothesized.
Purpose of the Study:
- To investigate the role of cardiolipin in thyroid hormone-induced changes in mitochondrial function.
- To determine if exogenous cardiolipin can restore decreased cytochrome oxidase activity in hypothyroid mitochondria.
Main Methods:
- Utilized the liposome-mitochondria fusion technique to increase cardiolipin content in mitochondria.
- Assessed cytochrome c oxidase activity in heart mitochondria from hypothyroid and control rats.
- Compared the effects of exogenous cardiolipin versus other phospholipids on enzyme activity.
Main Results:
- The decreased cytochrome c oxidase activity in hypothyroid rat heart mitochondria was significantly restored by adding exogenous cardiolipin.
- Other phospholipids did not restore the enzyme activity.
- The restoration of activity by cardiolipin was complete, reaching levels comparable to control rats.
Conclusions:
- Cardiolipin plays a critical role in regulating thyroid hormone-dependent changes in mitochondrial cytochrome oxidase activity.
- The data strongly support the involvement of cardiolipin in the functional alterations of mitochondria observed in hypothyroidism.
Abstract:
Cardiolipin plays an important role in mitochondrial membrane structure and function. We have recently reported a decrease in the cytochrome c oxidase activity in heart mitochondria from hypothyroid rats (G. Paradies et al. (1993) Arch. Biochem Biophys. 307, 91-95). A possible involvement of cardiolipin in such a decrease has been proposed. The aim of this work was to test our earlier proposal. We have investigated whether addition of exogenous cardiolipin to hypothyroid mitochondria is able to reverse, in situ, their decreased cytochrome oxidase activity. The method of fusion of liposomes with mitochondria developed by Hackenbrock (Hackenbrock and Chazotte (1986) Methods Enzymol. 125, 35-45) was employed in order to enrich the mitochondrial cardiolipin content. We demonstrate that the decreased activity of this enzyme complex in heart mitochondria from hypothyroid rats can be completely restored to the level of control rats by exogenously added cardiolipin but not by other phospholipids. These data provide strong evidence for the involvement of cardiolipin in the thyroid hormone induced changes of mitochondrial cytochrome oxidase activity.