Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, Rome, Italy.
Institute of Molecular Biology and Pathology, CNR, Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, Rome, Italy.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):129-137. doi: 10.1080/14756366.2019.1687461.
The 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme of the mevalonate pathway for the synthesis of cholesterol in mammals (ergosterol in fungi), is inhibited by statins, a class of cholesterol lowering drugs. Indeed, statins are in a wide medical use, yet statins treatment could induce side effects as hepatotoxicity and myopathy in patients. We used as a model to investigate the effects of statins on mitochondria. We demonstrate that statins are active in by lowering the ergosterol content in cells and interfering with the attachment of mitochondrial DNA to the inner mitochondrial membrane. Experiments on murine myoblasts confirmed these results in mammals. We propose that the instability of mitochondrial DNA is an early indirect target of statins.
3-羟-3-甲基戊二酰辅酶 A 还原酶是哺乳动物胆固醇合成（真菌中的麦角固醇）甲羟戊酸途径的关键酶，它被他汀类药物抑制，他汀类药物是一类降低胆固醇的药物。事实上，他汀类药物在广泛的医学用途中使用，但他汀类药物治疗可能会导致患者出现肝毒性和肌病等副作用。我们使用作为模型来研究他汀类药物对线粒体的影响。我们证明他汀类药物通过降低细胞中的麦角固醇含量并干扰线粒体 DNA 与线粒体内膜的附着来在中发挥作用。在鼠成肌细胞上的实验证实了这些在哺乳动物中的结果。我们提出线粒体 DNA 的不稳定性是他汀类药物的早期间接靶标。
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