Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria

Yasushi Tamura; Yoshihiro Harada; Shuh Ichi Nishikawa; Koji Yamano; Megumi Kamiya; Takuya Shiota; Takuya Kuroda; Osamu Kuge; Hiromi Sesaki; Kenichiro Imai; Kentaro Tomii; Toshiya Endo

doi:10.1016/j.cmet.2013.03.018

Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria

Yasushi Tamura, Yoshihiro Harada, Shuh Ichi Nishikawa, Koji Yamano, Megumi Kamiya, Takuya Shiota, Takuya Kuroda, Osamu Kuge, Hiromi Sesaki, Kenichiro Imai, Kentaro Tomii, Toshiya Endo

Organic and Biological Chemistry

Research output: Contribution to journal › Article › peer-review

114 Citations (Scopus)

Abstract

CDP-diacylglycerol (CDP-DAG) is central to the phospholipid biosynthesis pathways in cells. A prevailing view is that only one CDP-DAG synthase named Cds1 is present in both the endoplasmic reticulum (ER) and mitochondrial inner membrane (IM) and mediates generation of CDP-DAG from phosphatidic acid (PA) and CTP. However, we demonstrate here by using yeast Saccharomyces cerevisiae as a model organism that Cds1 resides in the ER but not in mitochondria, and that Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM. We also find that inositol depletion by overexpressing an arrestin-related protein Art5 partially restores the defects of cell growth and CL synthesis in the absence of Tam41. The present findings unveil the missing step of the cardiolipin synthesis pathway in mitochondria as well as the flexibile regulation of phospholipid biosynthesis to respond to compromised CDP-DAG synthesis in mitochondria.

Original language	English
Pages (from-to)	709-718
Number of pages	10
Journal	Cell metabolism
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2013.03.018
Publication status	Published - May 7 2013

All Science Journal Classification (ASJC) codes

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2013.03.018

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@article{ed85abcead5d47efa662e8dea0518d0d,

title = "Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria",

abstract = "CDP-diacylglycerol (CDP-DAG) is central to the phospholipid biosynthesis pathways in cells. A prevailing view is that only one CDP-DAG synthase named Cds1 is present in both the endoplasmic reticulum (ER) and mitochondrial inner membrane (IM) and mediates generation of CDP-DAG from phosphatidic acid (PA) and CTP. However, we demonstrate here by using yeast Saccharomyces cerevisiae as a model organism that Cds1 resides in the ER but not in mitochondria, and that Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM. We also find that inositol depletion by overexpressing an arrestin-related protein Art5 partially restores the defects of cell growth and CL synthesis in the absence of Tam41. The present findings unveil the missing step of the cardiolipin synthesis pathway in mitochondria as well as the flexibile regulation of phospholipid biosynthesis to respond to compromised CDP-DAG synthesis in mitochondria.",

author = "Yasushi Tamura and Yoshihiro Harada and Nishikawa, {Shuh Ichi} and Koji Yamano and Megumi Kamiya and Takuya Shiota and Takuya Kuroda and Osamu Kuge and Hiromi Sesaki and Kenichiro Imai and Kentaro Tomii and Toshiya Endo",

note = "Funding Information: We thank Dr. Nikolaus Pfanner for antibodies against Cds1. We are grateful to the members of the Endo lab for valuable discussions. K.I. is a research fellow of the Japan Society for the Promotion of Science (JSPS). We acknowledge support of this work by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) and the grant for CREST from Japan Science and Technology Agency (JST) to T.E.; a grant of the Platform for Drug Discovery, Informatics, and Structural Life Science from the MEXT to K.T.; and a NIH (GM089853) to H.S. ",

year = "2013",

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doi = "10.1016/j.cmet.2013.03.018",

language = "English",

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T1 - Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria

AU - Tamura, Yasushi

AU - Harada, Yoshihiro

AU - Nishikawa, Shuh Ichi

AU - Yamano, Koji

AU - Kamiya, Megumi

AU - Shiota, Takuya

AU - Kuroda, Takuya

AU - Kuge, Osamu

AU - Sesaki, Hiromi

AU - Imai, Kenichiro

AU - Tomii, Kentaro

AU - Endo, Toshiya

N1 - Funding Information: We thank Dr. Nikolaus Pfanner for antibodies against Cds1. We are grateful to the members of the Endo lab for valuable discussions. K.I. is a research fellow of the Japan Society for the Promotion of Science (JSPS). We acknowledge support of this work by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) and the grant for CREST from Japan Science and Technology Agency (JST) to T.E.; a grant of the Platform for Drug Discovery, Informatics, and Structural Life Science from the MEXT to K.T.; and a NIH (GM089853) to H.S.

PY - 2013/5/7

Y1 - 2013/5/7

N2 - CDP-diacylglycerol (CDP-DAG) is central to the phospholipid biosynthesis pathways in cells. A prevailing view is that only one CDP-DAG synthase named Cds1 is present in both the endoplasmic reticulum (ER) and mitochondrial inner membrane (IM) and mediates generation of CDP-DAG from phosphatidic acid (PA) and CTP. However, we demonstrate here by using yeast Saccharomyces cerevisiae as a model organism that Cds1 resides in the ER but not in mitochondria, and that Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM. We also find that inositol depletion by overexpressing an arrestin-related protein Art5 partially restores the defects of cell growth and CL synthesis in the absence of Tam41. The present findings unveil the missing step of the cardiolipin synthesis pathway in mitochondria as well as the flexibile regulation of phospholipid biosynthesis to respond to compromised CDP-DAG synthesis in mitochondria.

AB - CDP-diacylglycerol (CDP-DAG) is central to the phospholipid biosynthesis pathways in cells. A prevailing view is that only one CDP-DAG synthase named Cds1 is present in both the endoplasmic reticulum (ER) and mitochondrial inner membrane (IM) and mediates generation of CDP-DAG from phosphatidic acid (PA) and CTP. However, we demonstrate here by using yeast Saccharomyces cerevisiae as a model organism that Cds1 resides in the ER but not in mitochondria, and that Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM. We also find that inositol depletion by overexpressing an arrestin-related protein Art5 partially restores the defects of cell growth and CL synthesis in the absence of Tam41. The present findings unveil the missing step of the cardiolipin synthesis pathway in mitochondria as well as the flexibile regulation of phospholipid biosynthesis to respond to compromised CDP-DAG synthesis in mitochondria.

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JO - Cell Metabolism

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ER -

Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria

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