Mitochondria-type GPAT is required for mitochondrial fusion
Mitochondria-type GPAT is required for mitochondrial fusion
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DOI：
10.1038/emboj.2013.77
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发表时间：
2013-05-02
期刊：
影响因子：
11.4
通讯作者：
Arai, Hiroyuki
中科院分区：
文献类型：
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作者：
Ohba, Yohsuke;Sakuragi, Takeshi;Arai, Hiroyuki
甘油-3-磷酸酰基转移酶（GPAT）参与甘油脂质合成的第一步，并定位于内质网（ER）和线粒体中。为了阐明ER-GPAT和线粒体（Mt）-GPAT之间的功能差异，我们在C.并证明Mt-GPAT是线粒体融合所必需的。Mt-GPAT突变导致线粒体过度断裂。通过注射溶血磷脂酸（LPA）（GPAT的直接产物）和抑制LPA酰基转移酶（这两者都导致LPA在细胞中积累）来挽救缺陷。线粒体断裂的Mt-GPAT突变体中也获救的线粒体分裂蛋白DRP-1的抑制和线粒体融合蛋白FZO-1/mitofusin的过表达，这表明融合/分裂平衡的影响Mt-GPAT耗尽。线粒体碎片也观察到Mt-GPAT-耗尽的HeLa细胞。使用HeLa细胞的线粒体融合试验显示，Mt-GPAT缺失损害线粒体融合过程。我们从这些结果推测，由Mt-GPAT产生的LPA功能不仅作为甘油脂质合成的前体，而且作为线粒体融合的必要因素。
Glycerol-3-phosphate acyltransferase (GPAT) is involved in the first step in glycerolipid synthesis and is localized in both the endoplasmic reticulum (ER) and mitochondria. To clarify the functional differences between ER-GPAT and mitochondrial (Mt)-GPAT, we generated both GPAT mutants in C. elegans and demonstrated that Mt-GPAT is essential for mitochondrial fusion. Mutation of Mt-GPAT caused excessive mitochondrial fragmentation. The defect was rescued by injection of lysophosphatidic acid (LPA), a direct product of GPAT, and by inhibition of LPA acyltransferase, both of which lead to accumulation of LPA in the cells. Mitochondrial fragmentation in Mt-GPAT mutants was also rescued by inhibition of mitochondrial fission protein DRP-1 and by overexpression of mitochondrial fusion protein FZO-1/mitofusin, suggesting that the fusion/fission balance is affected by Mt-GPAT depletion. Mitochondrial fragmentation was also observed in Mt-GPAT-depleted HeLa cells. A mitochondrial fusion assay using HeLa cells revealed that Mt-GPAT depletion impaired mitochondrial fusion process. We postulate from these results that LPA produced by Mt-GPAT functions not only as a precursor for glycerolipid synthesis but also as an essential factor of mitochondrial fusion.