AMPK regulates Bcl2-L-13-mediated mitophagy induction for cardioprotection.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-11-23 DOI:10.1016/j.celrep.2024.115001

Tomokazu Murakawa, Jumpei Ito, Mara-Camelia Rusu, Manabu Taneike, Shigemiki Omiya, Javier Moncayo-Arlandi, Chiaki Nakanishi, Ryuta Sugihara, Hiroki Nishida, Kentaro Mine, Roland Fleck, Min Zhang, Kazuhiko Nishida, Ajay M Shah, Osamu Yamaguchi, Yasushi Sakata, Kinya Otsu

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引用次数: 0

Abstract

The accumulation of damaged mitochondria in the heart is associated with heart failure. Mitophagy is an autophagic degradation system that specifically targets damaged mitochondria. We have reported previously that Bcl2-like protein 13 (Bcl2-L-13) mediates mitophagy and mitochondrial fission in mammalian cells. However, the in vivo function of Bcl2-L-13 remains unclear. Here, we demonstrate that Bcl2-L-13-deficient mice and knockin mice, in which the phosphorylation site (Ser272) on Bcl2-L-13 was changed to Ala, showed left ventricular dysfunction in response to pressure overload. Attenuation of mitochondrial fission and mitophagy led to impairment of ATP production in these mouse hearts. In addition, we identified AMPKα2 as the kinase responsible for the phosphorylation of Bcl2-L-13 at Ser272. These results indicate that Bcl2-L-13 and its phosphorylation play an important role in maintaining cardiac function. Furthermore, the amplitude of stress-stimulated mitophagic activity could be modulated by AMPKα2.

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AMPK 可调控 Bcl2-L-13 介导的有丝分裂诱导，从而保护心脏。

心脏中受损线粒体的积累与心力衰竭有关。有丝分裂是一种自噬降解系统，专门针对受损线粒体。我们以前曾报道过 Bcl2 样蛋白 13（Bcl2-L-13）在哺乳动物细胞中介导有丝分裂和线粒体分裂。然而，Bcl2-L-13 在体内的功能仍不清楚。在这里，我们证明了 Bcl2-L-13 缺陷小鼠和基因敲除小鼠（Bcl2-L-13 的磷酸化位点（Ser272）变为 Ala）在压力过载时表现出左心室功能障碍。线粒体分裂和有丝分裂吞噬的减弱导致这些小鼠心脏的 ATP 生成受损。此外，我们还发现 AMPKα2 是导致 Bcl2-L-13 在 Ser272 处磷酸化的激酶。这些结果表明，Bcl2-L-13 及其磷酸化在维持心脏功能方面发挥着重要作用。此外，应激刺激的有丝分裂活性的幅度可由AMPKα2调节。

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.