Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain
Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain
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DOI：
10.1038/s41593-019-0556-3
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发表时间：
2020-01-01
影响因子：
25
通讯作者：
Surmeier, D. James
中科院分区：
文献类型：
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作者：
Graves, Steven M.;Xie, Zhong;Surmeier, D. James
单胺氧化酶（MAO）代谢胞质中的多巴胺（DA），从而限制自身氧化，但也被认为会产生胞质中的过氧化氢（H₂O₂）。我们表明，多巴胺的单胺氧化酶代谢不会增加胞质中的过氧化氢，而是导致线粒体电子传递链（ETC）的活性。这依赖于单胺氧化酶锚定在线粒体外膜上，并通过膜间隙传递电子，以支持阶段性多巴胺释放的生物能量需求。格雷夫斯等人证明，当神经递质多巴胺在释放位点在胞质中循环时，它可被一种线粒体酶代谢，以帮助产生维持突触功能所必需的能量。
Monoamine oxidase (MAO) metabolizes cytosolic dopamine (DA), thereby limiting auto-oxidation, but is also thought to generate cytosolic hydrogen peroxide (H2O2). We show that MAO metabolism of DA does not increase cytosolic H2O2 but leads to mitochondrial electron transport chain (ETC) activity. This is dependent upon MAO anchoring to the outer mitochondrial membrane and shuttling electrons through the intermembrane space to support the bioenergetic demands of phasic DA release. Graves et al. demonstrate that as the neurotransmitter dopamine cycles through the cytosol at release sites, it can be metabolized by a mitochondrial enzyme to help generate the energy necessary to sustain synaptic function.