对于AMPK来说,在调节不同的线粒道方面具有相反的作用
Marianna Longo1, Aniketh Bishnu1, Pierpaolo Risiglione1
1MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.
Molecular cell
|November 12, 2024
概括
由AMP激活的蛋白激酶 (AMPK) 调节了mitophagy. AMPK激活抑制了功能性线粒体的编程线粒体衰老,同时促进了受损线粒体的线粒体衰老.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体动力学的动力学
- 自自是一种自的过程.
背景情况:
- 线粒体的选择性降解,即线粒体的选择性降解,通常针对受损的细胞器.
- 然而,功能性线粒体也可以经历线粒体,这一过程称为编程线粒体,涉及NIX和BNIP3等受体.
- AMP激活蛋白激酶 (AMPK) 在编程线粒中的作用在很大程度上仍未被描述.
研究的目的:
- 为了研究AMPK在编程线粒中的作用.
- 阐明AMPK影响功能性线粒体和受损线粒体的线粒体衰变的分子机制.
主要方法:
- 在体内研究中利用细胞培养和mito-QC小鼠模型.
- 研究了线粒的途径,包括依赖NIX和脱极化诱导的线粒.
- 分析了蛋白质酸化事件,特别关注ULK1和帕金.
主要成果:
- AMPK通过在Ser556和Ser694酸化ULK1直接抑制NIX依赖的编程线粒,从而导致14-3-3介导的隔离.
- AMPK激活通过增加帕金酸化来增强受损线粒体的脱极化诱导的线粒细胞衰变,独立于ULK1.
- 这些发现在培养细胞和体内小鼠模型中得到了验证.
结论:
- AMPK的激活差异性地调节了线粒的途径.
- 通过ULK1的抑制,AMPK降低了功能性线粒体的线粒细胞衰变.
- 通过帕金激活,AMPK可以增强受损线粒体的线粒体.
相关概念视频
01:07MAPK Signaling Cascades
5.2K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.2K
01:19Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
01:19Translocation of Proteins into the Mitochondria
3.0K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
01:22PI3K/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
01:27Autophagy
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
03:03mTOR 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