Loss of MPC1 reprograms retinal metabolism to impair visual function
Loss of MPC1 reprograms retinal metabolism to impair visual function
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DOI：
10.1073/pnas.1812941116
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发表时间：
2019-02-26
影响因子：
11.1
通讯作者：
Du, Jianhai
中科院分区：
文献类型：
--
作者：
Grenell, Allison;Wang, Yekai;Du, Jianhai
脊椎动物视网膜中的葡萄糖代谢主要是有氧糖酵解（“Warburg效应”），这只允许一小部分葡萄糖衍生的丙酮酸进入线粒体。在这里，我们报告的证据表明，光感受器中被线粒体氧化的一小部分丙酮酸是视觉功能、光感受器结构和活力、正常的神经元-胶质相互作用和视网膜代谢稳态所必需的。线粒体丙酮酸载体（MPC）连接糖酵解和线粒体代谢。视网膜特异性MPC1缺失导致视网膜进行性变性和视杆和视锥光感受器视觉功能下降。利用靶向代谢组学和C-13示踪剂，我们发现MPC1是维持胞质还原能力、谷氨酰胺/谷氨酸代谢和燃料利用灵活性所必需的。
Glucose metabolism in vertebrate retinas is dominated by aerobic glycolysis (the "Warburg Effect"), which allows only a small fraction of glucose-derived pyruvate to enter mitochondria. Here, we report evidence that the small fraction of pyruvate in photoreceptors that does get oxidized by their mitochondria is required for visual function, photoreceptor structure and viability, normal neuron-glial interaction, and homeostasis of retinal metabolism. The mitochondrial pyruvate carrier (MPC) links glycolysis and mitochondrial metabolism. Retina-specific deletion of MPC1 results in progressive retinal degeneration and decline of visual function in both rod and cone photoreceptors. Using targeted-metabolomics and C-13 tracers, we found that MPC1 is required for cytosolic reducing power maintenance, glutamine/glutamate metabolism, and flexibility in fuel utilization.