Oxidation of fatty acids is the source of increased mitochondrial reactive oxygen species production in kidney cortical tubules in early diabetes.
Oxidation of fatty acids is the source of increased mitochondrial reactive oxygen species production in kidney cortical tubules in early diabetes.
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作者：
Rosca MG;Vazquez EJ;Chen Q;Kerner J;Kern TS;Hoppel CL
线粒体活性氧 (ROS) 会导致糖尿病患者的肾脏损伤。我们研究了链脲佐菌素诱导的大鼠 1 型糖尿病中肾皮质小管线粒体产生 ROS 的来源和位点。在糖尿病线粒体中，选择性脂肪酸氧化酶的数量和活性增加与脂肪酸底物的氧化磷酸化和净 ROS 产生增加相关（分别增加 40% 和 30%），而丙酮酸氧化减少，丙酮酸支持的 ROS 产生不变。在电子传输链 (ETC) 的特定位点提供电子的底物的氧化保持不变。脂肪酸氧化过程中 ROS 最大产量的增加不受限制从复合物 I 到复合物 III 的电子流的影响。复合物 III 中泛醇氧化位点产生 ROS 的最大能力在对照线粒体和糖尿病线粒体之间没有差异。总之，线粒体 ETC 既不是短期糖尿病肾小管线粒体中 ROS 产生的靶点也不是场所。线粒体脂肪酸氧化是净 ROS 产生增加的来源，电子泄漏位点位于电子转移黄素蛋白处靠近辅酶 Q 的位置，该黄素蛋白将电子从酰基辅酶 A 脱氢酶穿梭至辅酶 Q。
Mitochondrial reactive oxygen species (ROS) cause kidney damage in diabetes. We investigated the source and site of ROS production by kidney cortical tubule mitochondria in streptozotocin-induced type 1 diabetes in rats. In diabetic mitochondria, the increased amounts and activities of selective fatty acid oxidation enzymes is associated with increased oxidative phosphorylation and net ROS production with fatty acid substrates (by 40% and 30%, respectively), whereas pyruvate oxidation is decreased and pyruvate-supported ROS production is unchanged. Oxidation of substrates that donate electrons at specific sites in the electron transport chain (ETC) is unchanged. The increased maximal production of ROS with fatty acid oxidation is not affected by limiting the electron flow from complex I into complex III. The maximal capacity of the ubiquinol oxidation site in complex III in generating ROS does not differ between the control and diabetic mitochondria. In conclusion, the mitochondrial ETC is neither the target nor the site of ROS production in kidney tubule mitochondria in short-term diabetes. Mitochondrial fatty acid oxidation is the source of the increased net ROS production, and the site of electron leakage is located proximal to coenzyme Q at the electron transfer flavoprotein that shuttles electrons from acyl-CoA dehydrogenases to coenzyme Q.
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影响因子：
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