AMPK调节Bcl2-L-13介导的髓诱导,用于心脏保护
Tomokazu Murakawa1, Jumpei Ito2, Mara-Camelia Rusu3
1Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; The School of Cardiovascular Medicine and Sciences, King's College London British Heart Foundation Centre of Excellence, 125 Coldharbour Lane, SE5 9NU London, UK.
Cell reports
|November 24, 2024
概括
损坏的线粒体积累导致心力衰竭. 类似Bcl2的蛋白13 (Bcl2-L-13) 调节肌,对心脏功能和ATP产生至关重要,其由AMPKα2的酸化是关键.
科学领域:
- 心脏病学 心脏病学
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 损坏的线粒体的积累有助于心力衰竭.
- 线粒是一种关键的细胞过程,用于清除受损的线粒体.
- 众所周知,BCL2-样蛋白13 (Bcl2-L-13) 在体外中介于线粒体分裂和线粒体分裂.
研究的目的:
- 研究Bcl2-L-13在心脏健康中的体内功能.
- 阐明Bcl2-L-13酸化在压力下心脏功能中的作用.
- 为了确定负责Bcl2-L-13酸化的激酶.
主要方法:
- 产生和分析Bcl2-L-13缺乏和敲击小鼠 (Ser272Ala).
- 评估心脏功能,线粒体分裂和压力过载下的线粒体衰变.
- 使用生物化学测试识别负责Bcl2-L-13酸化的激酶.
主要成果:
- Bcl2-L-13缺乏和酸化受损导致左心室功能障碍.
- 线粒体分裂和线粒体分裂被减弱,损害了受影响心脏中的ATP产生.
- 鉴定出AMPKα2是Ser272.2.的酸化Bcl2-L-13的激酶.
结论:
- Bcl2-L-13及其AMPKα2的酸化对维持心脏功能至关重要.
- 这一途径对于线粒体质量控制和心脏能量生产至关重要.
- AMPKα2的活性调节了压力诱导的线粒,提供了一个潜在的治疗点.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
The Intrinsic Apoptotic Pathway
6.4K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
Autophagy
4.2K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K
Autophagic Cell Death
3.4K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
Electron Transport Chain: Complex I and II
11.7K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
11.7K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K


