Chávez Edmundo, Buelna-Chontal Mabel, Macías-López Arturo, Hernández-Esquivel Luz, Correa Francisco, Pavón Natalia
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez Ciudad de México, Mexico.
Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez Ciudad de México, Mexico.
Biochem Res Int. 2020 Dec 22;2020:5253108. doi: 10.1155/2020/5253108. eCollection 2020.
Mitochondrial permeability transition is characterized by the opening of a transmembranal pore that switches membrane permeability from specific to nonspecific. This structure allows the free traffic of ions, metabolites, and water across the mitochondrial inner membrane. The opening of the permeability transition pore is triggered by oxidative stress along with calcium overload. In this work, we explored if oxidative stress is a consequence, rather than an effector of the pore opening, by evaluating the interaction of agaric acid with the adenine nucleotide translocase, a structural component of the permeability transition pore. We found that agaric acid induces transition pore opening, increases the generation of oxygen-derived reactive species, augments the oxidation of unsaturated fatty acids in the membrane, and promotes the detachment of cytochrome c from the inner membrane. The effect of agaric acid was inhibited by the antioxidant tamoxifen in association with decreased binding of the thiol reagent eosin-3 maleimide to the adenine nucleotide translocase. We conclude that agaric acid promotes the opening of the pore, increasing ROS production that exerts oxidative modification of critical thiols in the adenine nucleotide translocase.
线粒体通透性转换的特征是跨膜孔开放，该孔将膜通透性从特异性转变为非特异性。这种结构允许离子、代谢物和水在线粒体内膜自由通行。通透性转换孔的开放由氧化应激以及钙超载触发。在这项研究中，我们通过评估木耳酸与腺嘌呤核苷酸转位酶（通透性转换孔的一种结构成分）的相互作用，探究氧化应激是否是孔开放的结果而非效应器。我们发现木耳酸诱导转换孔开放，增加氧衍生活性物质的生成，增强膜中不饱和脂肪酸的氧化，并促进细胞色素c从内膜脱离。抗氧化剂他莫昔芬抑制了木耳酸的作用，同时硫醇试剂曙红-3-马来酰亚胺与腺嘌呤核苷酸转位酶的结合减少。我们得出结论，木耳酸促进孔的开放，增加活性氧的产生，从而对腺嘌呤核苷酸转位酶中的关键硫醇进行氧化修饰。
