Brain mitochondria contain aquaporin water channels:: evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane
Brain mitochondria contain aquaporin water channels:: evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane
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DOI：
10.1096/fj.04-3515com
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发表时间：
2005-09-01
期刊：
影响因子：
4.8
通讯作者：
Ottersen, OP
中科院分区：
文献类型：
--
作者：
Amiry-Moghaddam, M;Lindland, H;Ottersen, OP
水通道蛋白是在动物、植物和微生物中发现的一种水通道。水通道蛋白的一个亚家族，即水甘油孔蛋白，对水以及某些溶质如甘油、乳酸和尿素具有渗透性。在这里，我们发现大脑中含有AQP9的两种同工异构体——一种具有特别广泛的底物特异性的水甘油三酯蛋白——这些同工异构体中更普遍的是在脑线粒体中表达的。在免疫印迹中检测到线粒体AQP9异构体为与25 kDa相似的条带。该异构体可能对应于通过选择性剪接获得的新的AQP9 mRNA，并且具有比肝脏异构体更短的ORF。亚分实验和高分辨率免疫金分析表明，这种新的AQP9亚型在线粒体内膜中富集。AQP9免疫阳性线粒体出现在整个大脑的星形胶质细胞和黑质、腹侧被盖区和弓形核的神经元亚群中。在后一种结构中，双标记免疫金电镜显示，AQP9免疫阳性的线粒体位于酪氨酸羟化酶免疫阳性的神经元中。我们的研究结果表明，线粒体AQP9是星形胶质细胞和中脑多巴胺能神经元的标志。在生理条件下，乳酸和其他代谢物通过AQP9的通量可能赋予线粒体优势，使线粒体能够适应线粒体外细胞质的代谢状态。我们假设多巴胺能神经元中线粒体AQP9的补体可能与帕金森病中这些神经元的易感性有关。
Aquaporins are a family of water channels found in animals, plants, and microorganisms. A subfamily of aquaporins, the aquaglyceroporins, are permeable for water as well as certain solutes such as glycerol, lactate, and urea. Here we show that the brain contains two isoforms of AQP9 - an aquaglyceroporin with a particularly broad substrate specificity - and that the more prevalent of these isoforms is expressed in brain mitochondria. The mitochondrial AQP9 isoform is detected as an similar to 25 kDa band in immunoblots. This isoform is likely to correspond to a new AQP9 mRNA that is obtained by alternative splicing and has a shorter ORF than the liver isoform. Subfractionation experiments and high-resolution immunogold analyses revealed that this novel AQP9 isoform is enriched in mitochondrial inner membranes. AQP9 immunopositive mitochondria occurred in astrocytes throughout the brain and in a subpopulation of neurons in the substantia nigra, ventral tegmental area, and arcuate nucleus. In the latter structures, the AQP9 immunopositive mitochondria were located in neurons that were also immunopositive for tyrosine hydroxylase, as demonstrated by double labeling immunogold electron microscopy. Our findings suggest that mitochondrial AQP9 is a hallmark of astrocytes and midbrain dopaminergic neurons. In physiological conditions, the flux of lactate and other metabolites through AQP9 may confer an advantage by allowing the mitochondria to adjust to the metabolic status of the extramitochondrial cytoplasm. We hypothesize that the complement of mitochondrial AQP9 in dopaminergic neurons may relate to the vulnerability of these neurons in Parkinson's disease.