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线粒体、自噬与年龄相关的神经退行性疾病:对复杂相互作用的新见解

Mitochondria, autophagy and age-associated neurodegenerative diseases: New insights into a complex interplay.

作者信息

Lionaki Eirini, Markaki Maria, Palikaras Konstantinos, Tavernarakis Nektarios

机构信息

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece.

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Crete, Greece; Department of Biology, University of Crete, Heraklion, Crete, Greece.

出版信息

Biochim Biophys Acta. 2015 Nov;1847(11):1412-23. doi: 10.1016/j.bbabio.2015.04.010. Epub 2015 Apr 24.

Abstract

Mitochondria represent the major bioenergetic hub coordinating cellular and organismal homeostasis. The underlying causes of many pathologies tormenting humans converge on impaired mitochondrial maintenance. Mitochondria-specific autophagy (mitophagy), a cellular catabolic process targeting mitochondria, holds a prominent role in mitochondrial quality control. In addition to core autophagic machinery components, mitophagy exploits a variety of molecules that identify damaged or superfluous mitochondria and mediate their elimination. Signaling pathways integrating environmental and genetic stimuli interact with key mitophagy effectors to activate cellular stress response mechanisms, ultimately modulating health and lifespan. Here, we review the signaling cascades and molecular mechanisms that govern the process of mitophagy and discuss their involvement in ageing and neurodegeneration. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.

摘要

线粒体是协调细胞和机体稳态的主要生物能量枢纽。许多困扰人类的疾病的根本原因都集中在线粒体维持受损上。线粒体特异性自噬(线粒体自噬)是一种针对线粒体的细胞分解代谢过程,在线粒体质量控制中起着重要作用。除了核心自噬机制成分外,线粒体自噬还利用多种分子来识别受损或多余的线粒体并介导其清除。整合环境和遗传刺激的信号通路与关键的线粒体自噬效应器相互作用,以激活细胞应激反应机制,最终调节健康和寿命。在这里,我们综述了调控线粒体自噬过程的信号级联和分子机制,并讨论了它们在衰老和神经退行性变中的作用。本文是名为《衰老中的线粒体功能障碍》的特刊的一部分。

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