Statins interfere with the attachment of S. cerevisiae mtDNA to the inner mitochondrial membrane
Statins interfere with the attachment of S. cerevisiae mtDNA to the inner mitochondrial membrane
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DOI：
10.1080/14756366.2019.1687461
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发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Rinaldi, Teresa
中科院分区：
文献类型：
--
作者：
Cirigliano, Angela;Amelina, Antonia;Rinaldi, Teresa
3-羟基-3-甲基戊二酰辅酶A还原酶是哺乳动物合成胆固醇(真菌中的麦角甾醇)甲氧戊酸途径的关键酶，它被降胆固醇药物他汀类药物抑制。事实上，他汀类药物在医学上有广泛的用途，但他汀类药物的治疗可能会导致副作用，如肝脏毒性和患者的肌病。我们以酿酒酵母为模型，研究他汀类药物对线粒体的影响。我们证明了他汀类药物在酿酒酵母中的活性，它通过降低细胞中麦角甾醇的含量和干扰线粒体DNA与线粒体膜的附着而发挥作用。对小鼠成肌细胞的实验证实了哺乳动物的这些结果。我们认为线粒体DNA的不稳定性是他汀类药物的早期间接靶点。
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 Saccharomyces cerevisiae as a model to investigate the effects of statins on mitochondria. We demonstrate that statins are active in S.cerevisiae 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.