Mitochondrial complex I as a novel target for intraneuronal DA: Modulation of respiration in intact cells
Mitochondrial complex I as a novel target for intraneuronal DA: Modulation of respiration in intact cells
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DOI：
10.1016/j.bcp.2009.03.024
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发表时间：
2009-07-01
影响因子：
5.8
通讯作者：
Ben-Shachar, Dorit
中科院分区：
文献类型：
--
作者：
Brenner-Lavie, Hanit;Klein, Ehud;Ben-Shachar, Dorit
越来越多的证据表明线粒体在突触增强和神经传递以及棘和突触的形态发生和可塑性中发挥作用。然而，研究神经递质相互影响线粒体功能的能力的研究很少。在本研究中，我们研究了多巴胺是否可以影响完整神经元细胞中的线粒体功能。我们已经证明，人神经母细胞瘤 SH-SY5Y 细胞短期或长期暴露于多巴胺 (DA) 会抑制线粒体呼吸。这种抑制与细胞内 DA 水平的增加有关，并且可以被 DA 膜转运蛋白抑制剂、可卡因和 GBR-12909 阻止。 DA 抑制通过复合物 I 驱动的呼吸，但不通过复合物 II 或 III 驱动，这与 DA 特异性抑制线粒体制剂中复合物 I 活性的能力一致。 DA 对复合物 I 的影响与复合物 I 三个亚基表达的改变无关，之前报道这些亚基在 DA 相关病理学中异常。 DA 对呼吸的影响并不是由于其形成活性氧的能力。抗精神病药物与 DA 受体竞争并抑制复合物 I 活性，也会降低复合物 I 驱动的线粒体呼吸。这些发现可能表明，被神经元吸收的 DA 可以影响线粒体，从而影响神经传递和突触可塑性。这种机制可能与 DA 相关的非退行性病理学（例如精神分裂症）有关。 (c) 2009 Elsevier Inc. 保留所有权利。
Accumulating evidence suggests a role for mitochondria in synaptic potentiation and neurotransmission as well as in morphogenesis and plasticity of spines and synapses. However, studies investigating the ability of neurotransmitters to reciprocally affect mitochondrial function are sparse. In the present study we investigated whether dopamine can affect mitochondrial function in intact neuronal cells. We have shown that short- or long-term exposure of human neuroblastoma SH-SY5Y cells to dopamine (DA) inhibited mitochondrial respiration. This inhibition was associated with an increase in DA intracellular levels, and was prevented by the DA membrane transporter inhibitors, cocaine and GBR-12909. DA inhibited respiration driven through complex I but not through complexes II or III, in line with DA ability to specifically inhibit complex I activity in mitochondrial preparations. The effect of DA on complex I was not associated with altered expression of three subunits of complex I, which were formerly reported abnormal in DA-related pathologies. DA effects on respiration were not due to its ability to form reactive oxygen species. Antipsychotic drugs, which compete with DA on its receptors and inhibit complex I activity, also decreased complex I driven mitochondrial respiration. These findings may suggest that DA, which is taken up by neurons, can affect mitochondria and thereby neurotransmission and synaptic plasticity. Such a mechanism may be of relevance to DA-related non-degenerative pathologies such as schizophrenia. (c) 2009 Elsevier Inc. All rights reserved.