Departamento de Bioquímica, Biología Molecular y Celular. Universidad de Zaragoza, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain; Centro de Investigaciones Biomédicas En Red de Enfermedades Raras (CIBERER), Zaragoza, Spain.
Departamento de Bioquímica, Biología Molecular y Celular. Universidad de Zaragoza, Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain.
Food Chem Toxicol. 2018 Oct;120:89-97. doi: 10.1016/j.fct.2018.07.014. Epub 2018 Jul 6.
Mitochondrial DNA mutations in genes encoding respiratory complex I polypeptides can cause Leber hereditary optic neuropathy. Toxics affecting oxidative phosphorylation system can also cause mitochondrial optic neuropathy. Some complex I inhibitors found in edible plants might differentially interact with these pathologic mutations and modify their penetrance. To analyze this interaction, we have compared the effect of rotenone, capsaicin and rolliniastatin-1 on cybrids harboring the most frequent Leber hereditary optic neuropathy mutations and found that m.3460G > A mutation increases rotenone resistance but capsaicin and rolliniastatin-1 susceptibility. Thus, to explain the pathogenicity of mitochondrial diseases due to mitochondrial DNA mutations, their potential interactions with environment factors will have to be considered.
线粒体 DNA 突变导致编码呼吸复合物 I 多肽的基因突变可引起莱伯遗传性视神经病变。影响氧化磷酸化系统的毒物也可引起线粒体视神经病变。一些在食用植物中发现的复合物 I 抑制剂可能与这些病理性突变发生不同的相互作用，并改变其外显率。为了分析这种相互作用，我们比较了鱼藤酮、辣椒素和 rolliniastatin-1 对携带最常见莱伯遗传性视神经病变突变的杂种细胞的影响，发现 m.3460G > A 突变增加了鱼藤酮的耐药性，但增加了辣椒素和 rolliniastatin-1 的敏感性。因此，为了解释由于线粒体 DNA 突变引起的线粒体疾病的发病机制，必须考虑它们与环境因素的潜在相互作用。
