期刊
EMBO JOURNAL
卷 32, 期 9, 页码 1265-1279出版社
WILEY
DOI: 10.1038/emboj.2013.77
关键词
C. elegans; fusion; glycerol-3-phosphate acyltransferase; lysophosphatidic acid; mitochondria
资金
- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency
- Program for Promotion of Basic and Applied Research for Innovations in Bio-Oriented Industry
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
- Japanese Ministry of Health, Labor, and Welfare
- Grants-in-Aid for Scientific Research [12J10377, 24390053, 24790092, 23227004, 23790256, 24790064] Funding Source: KAKEN
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.
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