Statins interfere with the attachment of S. cerevisiae mtDNA to the inner mitochondrial membrane

Journal of Enzyme Inhibition and Medicinal Chemistry

卷:35

Chiara Mozzetta¹  Antonia Amelina¹  Angela Cirigliano¹  Beatrice Biferali¹  Michele Maria Bianchi¹  Rodolfo Negri¹  Teresa Rinaldi¹  Elah Pick²  Mattia Mori³  Bruno Botta⁴  Alberto Macone⁵ 

[1] Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of Rome;

[2] Department of Biology and Environment, Faculty of Natural Sciences, University of Haifa at Oranim;

[3] Department of Biotechnology, Chemistry and Pharmacy, University of Siena;

[4] Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome;

[5] Pasteur Institute-Cenci Bolognetti Foundation;

关键词: statins;    ergosterol;    cholesterol;    mitochondrial dna;    myopathy;   

DOI  :  10.1080/14756366.2019.1687461

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown