PGAM5 is an MFN2 phosphatase that plays an essential role in the regulation of mitochondrial dynamics.

IF 6.9 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2023-08-29 DOI:10.1016/j.celrep.2023.112895

Sudeshna Nag, Kaitlin Szederkenyi, Olena Gorbenko, Hannah Tyrrell, Christopher M Yip, G Angus McQuibban

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引用次数: 1

Abstract

Mitochondrial morphology is regulated by the post-translational modifications of the dynamin family GTPase proteins including mitofusin 1 (MFN1), MFN2, and dynamin-related protein 1 (DRP1). Mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5) is emerging as a regulator of these post-translational modifications; however, its precise role in the regulation of mitochondrial morphology is unknown. We show that PGAM5 interacts with MFN2 and DRP1 in a stress-sensitive manner. PGAM5 regulates MFN2 phosphorylation and consequently protects it from ubiquitination and degradation. Further, phosphorylation and dephosphorylation modification of MFN2 regulates its fusion ability. Phosphorylation enhances fission and degradation, whereas dephosphorylation enhances fusion. PGAM5 dephosphorylates MFN2 to promote mitochondrial network formation. Further, using a Drosophila genetic model, we demonstrate that the MFN2 homolog Marf and dPGAM5 are in the same biological pathway. Our results identify MFN2 dephosphorylation as a regulator of mitochondrial fusion and PGAM5 as an MFN2 phosphatase.

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PGAM5是一种MFN2磷酸酶，在线粒体动力学调节中起重要作用。

线粒体形态受动力蛋白家族GTPase蛋白的翻译后修饰调控，包括mitofusin 1 (MFN1)、MFN2和动力蛋白相关蛋白1 (DRP1)。线粒体磷酸酶磷酸甘油酸突变酶5 (PGAM5)正在成为这些翻译后修饰的调节因子;然而，其在线粒体形态调控中的确切作用尚不清楚。我们发现PGAM5以应激敏感的方式与MFN2和DRP1相互作用。PGAM5调节MFN2磷酸化，从而保护其免于泛素化和降解。此外，MFN2的磷酸化和去磷酸化修饰调节其融合能力。磷酸化促进裂变和降解，而去磷酸化促进融合。PGAM5去磷酸化MFN2，促进线粒体网络的形成。此外，利用果蝇遗传模型，我们证明了MFN2同源Marf和dPGAM5在相同的生物学途径中。我们的研究结果确定MFN2去磷酸化是线粒体融合的调节因子，PGAM5是MFN2磷酸酶。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.