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Atg1 与线粒体功能、内吞作用、生长和发育的多方面相互作用。

The Multifaceted Interactions of Atg1 with Mitochondrial Function, Endocytosis, Growth, and Development.

机构信息

Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, Melbourne 3086, Australia.

出版信息

Cells. 2024 Jul 14;13(14):1191. doi: 10.3390/cells13141191.

Abstract

Autophagy is a degradative recycling process central to the maintenance of homeostasis in all eukaryotes. By ensuring the degradation of damaged mitochondria, it plays a key role in maintaining mitochondrial health and function. Of the highly conserved autophagy proteins, autophagy-related protein 1 (Atg1) is essential to the process. The involvement of these proteins in intracellular signalling pathways, including those involving mitochondrial function, are still being elucidated. Here the role of Atg1 was investigated in the simple model organism using an null mutant and mutants overexpressing or antisense-inhibiting . When evaluated against the well-characterised outcomes of mitochondrial dysfunction in this model, altered expression resulted in an unconventional set of phenotypic outcomes in growth, endocytosis, multicellular development, and mitochondrial homeostasis. The findings here show that Atg1 is involved in a tightly regulated signal transduction pathway coordinating energy-consuming processes such as cell growth and multicellular development, along with nutrient status and energy production. Furthermore, Atg1's effects on energy homeostasis indicate a peripheral ancillary role in the mitochondrial signalling network, with effects on energy balance rather than direct effects on electron transport chain function. Further research is required to tease out these complex networks. Nevertheless, this study adds further evidence to the theory that autophagy and mitochondrial signalling are not opposing but rather linked, yet strictly controlled, homeostatic mechanisms.

摘要

自噬是所有真核生物维持体内平衡的核心降解回收过程。通过确保受损线粒体的降解,它在维持线粒体健康和功能方面发挥着关键作用。在高度保守的自噬蛋白中,自噬相关蛋白 1(Atg1)对该过程至关重要。这些蛋白质在细胞内信号通路中的作用,包括涉及线粒体功能的信号通路,仍在阐明之中。在这里,使用 null 突变体和过表达或反义抑制突变体,在简单的模式生物 中研究了 Atg1 的作用。当根据该模型中线粒体功能障碍的特征性结果进行评估时,改变 的表达导致了一系列非常规的表型结果,包括生长、内吞作用、多细胞发育和线粒体动态平衡。这些发现表明,Atg1 参与了一个严格调控的信号转导途径,协调着细胞生长和多细胞发育等耗能过程,以及营养状态和能量产生。此外,Atg1 对能量平衡的影响表明其在线粒体信号网络中具有外围辅助作用,对能量平衡的影响而不是对电子传递链功能的直接影响。需要进一步的研究来梳理这些复杂的网络。然而,这项研究为自噬和线粒体信号之间不是对立的,而是相互联系但又严格控制的内稳态机制这一理论提供了更多证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9b0/11274416/d488b7a851d8/cells-13-01191-g001.jpg

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