Department of Physiology, University of California at San Francisco, San Francisco, California 94158, USA.
Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94158, USA.
Genes Dev. 2021 Apr 1;35(7-8):449-469. doi: 10.1101/gad.346759.120.
Our cells are comprised of billions of proteins, lipids, and other small molecules packed into their respective subcellular organelles, with the daunting task of maintaining cellular homeostasis over a lifetime. However, it is becoming increasingly evident that organelles do not act as autonomous discrete units but rather as interconnected hubs that engage in extensive communication through membrane contacts. In the last few years, our understanding of how these contacts coordinate organelle function has redefined our view of the cell. This review aims to present novel findings on the cellular interorganelle communication network and how its dysfunction may contribute to aging and neurodegeneration. The consequences of disturbed interorganellar communication are intimately linked with age-related pathologies. Given that both aging and neurodegenerative diseases are characterized by the concomitant failure of multiple cellular pathways, coordination of organelle communication and function could represent an emerging regulatory mechanism critical for long-term cellular homeostasis. We anticipate that defining the relationships between interorganelle communication, aging, and neurodegeneration will open new avenues for therapeutics.
我们的细胞由数十亿个蛋白质、脂质和其他小分子组成，这些分子被包装到各自的亚细胞细胞器中，它们面临着在一生中维持细胞内环境稳定的艰巨任务。然而，越来越明显的是，细胞器并不是作为自主离散的单元发挥作用，而是作为相互连接的枢纽，通过膜接触进行广泛的交流。在过去的几年中，我们对这些联系如何协调细胞器功能的理解已经重新定义了我们对细胞的看法。这篇综述旨在介绍细胞内细胞器间通讯网络的新发现，以及其功能障碍如何导致衰老和神经退行性变。细胞器间通讯中断的后果与与年龄相关的病理密切相关。鉴于衰老和神经退行性疾病的特征是多种细胞途径的同时失效，协调细胞器通讯和功能可能代表着一种新兴的调节机制，对长期细胞内环境稳定至关重要。我们预计，定义细胞器间通讯、衰老和神经退行性变之间的关系将为治疗开辟新途径。
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