Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver

Abstract Palmitoyltransferase (PAT) catalyses protein S-palmitoylation which adds 16-carbon palmitate to specific cysteines and contributes to various biological functions. We previously reported that in mice, deficiency of Zdhhc13, a member of the PAT family, causes severe phenotypes including amyl...

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Autores principales:	Li-Fen Shen, Yi-Ju Chen, Kai-Ming Liu, Amir N. Saleem Haddad, I-Wen Song, Hsiao-Yuh Roan, Li-Ying Chen, Jeffrey J. Y. Yen, Yu-Ju Chen, Jer-Yuarn Wu, Yuan-Tsong Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e35ebf112478465f9fd601e2687b7dd7
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spelling	oai:doaj.org-article:e35ebf112478465f9fd601e2687b7dd72021-12-02T16:07:02ZRole of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver10.1038/s41598-017-02159-42045-2322https://doaj.org/article/e35ebf112478465f9fd601e2687b7dd72017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02159-4https://doaj.org/toc/2045-2322Abstract Palmitoyltransferase (PAT) catalyses protein S-palmitoylation which adds 16-carbon palmitate to specific cysteines and contributes to various biological functions. We previously reported that in mice, deficiency of Zdhhc13, a member of the PAT family, causes severe phenotypes including amyloidosis, alopecia, and osteoporosis. Here, we show that Zdhhc13 deficiency results in abnormal liver function, lipid abnormalities, and hypermetabolism. To elucidate the molecular mechanisms underlying these disease phenotypes, we applied a site-specific quantitative approach integrating an alkylating resin-assisted capture and mass spectrometry-based label-free strategy for studying the liver S-palmitoylome. We identified 2,190 S-palmitoylated peptides corresponding to 883 S-palmitoylated proteins. After normalization using the membrane proteome with TMT10-plex labelling, 400 (31%) of S-palmitoylation sites on 254 proteins were down-regulated in Zdhhc13-deficient mice, representing potential ZDHHC13 substrates. Among these, lipid metabolism and mitochondrial dysfunction proteins were overrepresented. MCAT and CTNND1 were confirmed to be specific ZDHHC13 substrates. Furthermore, we found impaired mitochondrial function in hepatocytes of Zdhhc13-deficient mice and Zdhhc13-knockdown Hep1–6 cells. These results indicate that ZDHHC13 is an important regulator of mitochondrial activity. Collectively, our study allows for a systematic view of S-palmitoylation for identification of ZDHHC13 substrates and demonstrates the role of ZDHHC13 in mitochondrial function and metabolism in liver.Li-Fen ShenYi-Ju ChenKai-Ming LiuAmir N. Saleem HaddadI-Wen SongHsiao-Yuh RoanLi-Ying ChenJeffrey J. Y. YenYu-Ju ChenJer-Yuarn WuYuan-Tsong ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li-Fen Shen Yi-Ju Chen Kai-Ming Liu Amir N. Saleem Haddad I-Wen Song Hsiao-Yuh Roan Li-Ying Chen Jeffrey J. Y. Yen Yu-Ju Chen Jer-Yuarn Wu Yuan-Tsong Chen Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver
description	Abstract Palmitoyltransferase (PAT) catalyses protein S-palmitoylation which adds 16-carbon palmitate to specific cysteines and contributes to various biological functions. We previously reported that in mice, deficiency of Zdhhc13, a member of the PAT family, causes severe phenotypes including amyloidosis, alopecia, and osteoporosis. Here, we show that Zdhhc13 deficiency results in abnormal liver function, lipid abnormalities, and hypermetabolism. To elucidate the molecular mechanisms underlying these disease phenotypes, we applied a site-specific quantitative approach integrating an alkylating resin-assisted capture and mass spectrometry-based label-free strategy for studying the liver S-palmitoylome. We identified 2,190 S-palmitoylated peptides corresponding to 883 S-palmitoylated proteins. After normalization using the membrane proteome with TMT10-plex labelling, 400 (31%) of S-palmitoylation sites on 254 proteins were down-regulated in Zdhhc13-deficient mice, representing potential ZDHHC13 substrates. Among these, lipid metabolism and mitochondrial dysfunction proteins were overrepresented. MCAT and CTNND1 were confirmed to be specific ZDHHC13 substrates. Furthermore, we found impaired mitochondrial function in hepatocytes of Zdhhc13-deficient mice and Zdhhc13-knockdown Hep1–6 cells. These results indicate that ZDHHC13 is an important regulator of mitochondrial activity. Collectively, our study allows for a systematic view of S-palmitoylation for identification of ZDHHC13 substrates and demonstrates the role of ZDHHC13 in mitochondrial function and metabolism in liver.
format	article
author	Li-Fen Shen Yi-Ju Chen Kai-Ming Liu Amir N. Saleem Haddad I-Wen Song Hsiao-Yuh Roan Li-Ying Chen Jeffrey J. Y. Yen Yu-Ju Chen Jer-Yuarn Wu Yuan-Tsong Chen
author_facet	Li-Fen Shen Yi-Ju Chen Kai-Ming Liu Amir N. Saleem Haddad I-Wen Song Hsiao-Yuh Roan Li-Ying Chen Jeffrey J. Y. Yen Yu-Ju Chen Jer-Yuarn Wu Yuan-Tsong Chen
author_sort	Li-Fen Shen
title	Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver
title_short	Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver
title_full	Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver
title_fullStr	Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver
title_full_unstemmed	Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver
title_sort	role of s-palmitoylation by zdhhc13 in mitochondrial function and metabolism in liver
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e35ebf112478465f9fd601e2687b7dd7
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Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver

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