<b>AMPK regulates Bcl2-L-13-mediated mitophagy induction for cardioprotection</b>

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 previously reported that Bcl2-like protein 13 (Bcl2-L-13) mediates mitophagy and mitochondrial fission in mammalian cells. However, the <i>in vivo</i> function of Bcl2-L-13 remains unclear. Here, we demonstrate that Bcl2-L-13-deficient mice and knock-in 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 AMPKa2 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 AMPKa2.心脏内受损线粒体的蓄积与心力衰竭密切相关。线粒体自噬（Mitophagy）是一种特异性靶向受损线粒体的自噬降解系统。此前我们曾报道，Bcl2样蛋白13（Bcl2-L-13）可介导哺乳动物细胞中的线粒体自噬与线粒体分裂过程。然而，Bcl2-L-13的体内（in vivo）功能仍未明确。本研究中，我们证实，Bcl2-L-13基因敲除小鼠以及将Bcl2-L-13上的磷酸化位点Ser272突变为丙氨酸（Ala）的定点敲入小鼠，在受到压力超负荷刺激时均出现左心室功能障碍。线粒体分裂与线粒体自噬的减弱会导致这些小鼠心脏的ATP生成能力受损。此外，我们确定了负责催化Bcl2-L-13在Ser272位点发生磷酸化的激酶为腺苷酸活化蛋白激酶α2（AMPKa2）。上述结果表明，Bcl2-L-13及其磷酸化修饰在维持心脏正常功能中发挥关键作用。进一步研究发现，应激刺激诱导的线粒体自噬活性强度可通过AMPKa2进行调控。

搜集汇总

背景与挑战

背景概述

该数据集包含一项关于AMPK调控Bcl2-L-13介导的线粒体自噬以促进心脏保护的研究数据，主要涉及小鼠模型中的实验图表和原始文件。数据集通过分析Bcl2-L-13缺陷和磷酸化位点突变小鼠，揭示了AMPKα2在磷酸化Bcl2-L-13中的关键作用，以及这对线粒体分裂、自噬和心脏功能维持的重要性。