Succinate Can Shuttle Reducing Power from the Hypoxic Retina to the O2-Rich Pigment Epithelium
Succinate Can Shuttle Reducing Power from the Hypoxic Retina to the O2-Rich Pigment Epithelium
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DOI：
10.1016/j.celrep.2020.107606
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发表时间：
2020-05-05
期刊：
影响因子：
8.8
通讯作者：
Hurley, James B.
中科院分区：
文献类型：
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作者：
Bisbach, Celia M.;Hass, Daniel T.;Hurley, James B.
当 O-2 充足时，线粒体电子传递链将其用作末端电子受体。然而，哺乳动物的视网膜在眼睛缺氧的环境中茁壮成长。我们发现视网膜中的线粒体通过逆转琥珀酸脱氢酶反应以使用富马酸而不是 O-2 接受电子来适应缺氧环境。逆向琥珀酸脱氢酶活性产生琥珀酸，并通过缺氧诱导的细胞色素氧化酶下调而增强。视网膜可以将它们产生的琥珀酸输出到邻近富含 O-2 的视网膜色素上皮-脉络膜复合体。在那里，琥珀酸使 O-2 消耗成倍增加。然后，色素上皮中由琥珀酸制成的苹果酸可以被输入视网膜，在视网膜中转化为富马酸，在逆琥珀酸脱氢酶反应中再次接受电子。这种苹果酸-琥珀酸穿梭机可以通过将还原力从缺乏 O-2 的组织（视网膜）转移到富含 O-2 的组织（视网膜色素上皮-脉络膜）来维持这两种组织。
When O-2 is plentiful, the mitochondrial electron transport chain uses it as a terminal electron acceptor. However, the mammalian retina thrives in a hypoxic niche in the eye. We find that mitochondria in retinas adapt to their hypoxic environment by reversing the succinate dehydrogenase reaction to use fumarate to accept electrons instead of O-2. Reverse succinate dehydrogenase activity produces succinate and is enhanced by hypoxia-induced downregulation of cytochrome oxidase. Retinas can export the succinate they produce to the neighboring O-2-rich retinal pigment epithelium-choroid complex. There, succinate enhances O-2 consumption by severalfold. Malate made from succinate in the pigment epithelium can then be imported into the retina, where it is converted to fumarate to again accept electrons in the reverse succinate dehydrogenase reaction. This malate-succinate shuttle can sustain these two tissues by transferring reducing power from an O-2-poor tissue (retina) to an O-2-rich one (retinal pigment epithelium-choroid).