Glycolysis, but not Mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes.
Glycolysis, but not Mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes.
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DOI：
10.1038/srep18575
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发表时间：
2015-12-18
影响因子：
4.6
通讯作者：
Nakagawa T
中科院分区：
文献类型：
--
作者：
Ozawa S;Ueda S;Imamura H;Mori K;Asanuma K;Yanagita M;Nakagawa T
分化的足细胞是肾小球细胞的一种，需要大量的能量来维持肾小球的生理。线粒体和糖酵解是ATP的两个主要生产者，但它们在足细胞中的确切作用尚不清楚。本研究评估了线粒体和糖酵解在足细胞分化和分化中的作用。分化后的足细胞线粒体位于细胞体中央，封闭线粒体对细胞形态和迁移能力影响不大。相反，阻断糖酵解显著减少这些细胞的皮质区片状脂膜的形成，降低细胞的迁移能力并诱导细胞凋亡。一直以来，片状脂肪体内的局部ATP产生主要受糖酵解的调节。反过来，通过阻断线粒体呼吸或糖酵解，突触素的表达得到改善。与分化的足细胞类似，分化的足细胞利用糖酵解来调节细胞凋亡和片状脂肪的形成，而突触素的表达可能参与线粒体OXPHOS和糖酵解。最后，成年小鼠足细胞的大部分线粒体主要在胞浆中心，而磷酸果糖激酶，一种糖酵解的限速酶，在足突中表达。这些数据表明，线粒体和糖酵解在分化和分化的足细胞中发挥着平行但不同的作用。
Differentiated podocytes, a type of renal glomerular cells, require substantial levels of energy to maintain glomerular physiology. Mitochondria and glycolysis are two major producers of ATP, but the precise roles of each in podocytes remain unknown. This study evaluated the roles of mitochondria and glycolysis in differentiated and differentiating podocytes. Mitochondria in differentiated podocytes are located in the central part of cell body while blocking mitochondria had minor effects on cell shape and migratory ability. In contrast, blocking glycolysis significantly reduced the formation of lamellipodia, a cortical area of these cells, decreased the cell migratory ability and induced the apoptosis. Consistently, the local ATP production in lamellipodia was predominantly regulated by glycolysis. In turn, synaptopodin expression was ameliorated by blocking either mitochondrial respiration or glycolysis. Similar to differentiated podocytes, the differentiating podocytes utilized the glycolysis for regulating apoptosis and lamellipodia formation while synaptopodin expression was likely involved in both mitochondrial OXPHOS and glycolysis. Finally, adult mouse podocytes have most of mitochondria predominantly in the center of the cytosol whereas phosphofructokinase, a rate limiting enzyme for glycolysis, was expressed in foot processes. These data suggest that mitochondria and glycolysis play parallel but distinct roles in differentiated and differentiating podocytes.