Mitochondria‐type GPAT is required for mitochondrial fusion |
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Authors: | Yohsuke Ohba Eriko Kage‐Nakadai Naoko H Tomioka Nozomu Kono Rieko Imae Asuka Inoue Junken Aoki Naotada Ishihara Shohei Mitani Hiroyuki Arai |
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Affiliation: | 1. Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, , Tokyo, Japan;2. Department of Physiology, Tokyo Women's Medical University School of Medicine, , Tokyo, Japan;3. CREST, Japan Science and Technology Agency (JST), , Tokyo, Japan;4. Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, , Sendai, Japan;5. Department of Protein Biochemistry, Institute of Life Science, Kurume University, , Kurume, Japan |
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Abstract: | 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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Keywords: | C. elegans fusion glycerol‐3‐phosphate acyltransferase lysophosphatidic acid mitochondria |
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