Li Yu, Qi Jinxin, Guo Linhong, Jiang Xian, He Gu
Department of Dermatology & Venerology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Aging Cell. 2025 Jan;24(1):e14447. doi: 10.1111/acel.14447. Epub 2024 Dec 12.
Organellar homeostasis and crosstalks within a cell have emerged as essential regulatory and determining factors for the survival and functions of cells. In response to various stimuli, cells can activate the organellar quality control systems (QCS) to maintain homeostasis. Numerous studies have demonstrated that dysfunction of QCS can lead to various aging-related diseases such as neurodegenerative, pulmonary, cardiometabolic diseases and cancers. However, the interplay between QCS and their potential role in these diseases are poorly understood. In this review, we present an overview of the current findings of QCS and their crosstalk, encompassing mitochondria, endoplasmic reticulum, Golgi apparatus, ribosomes, peroxisomes, lipid droplets, and lysosomes as well as the aberrant interplays among these organelles that contributes to the onset and progression of aging-related disorders. Furthermore, potential therapeutic approaches based on these quality control interactions are discussed. Our perspectives can enhance insights into the regulatory networks underlying QCS and the pathology of aging and aging-related diseases, which may pave the way for the development of novel therapeutic targets.
细胞内的细胞器稳态及相互作用已成为细胞生存和功能的重要调节及决定因素。响应各种刺激时，细胞可激活细胞器质量控制系统（QCS）以维持稳态。大量研究表明，QCS功能障碍可导致各种与衰老相关的疾病，如神经退行性疾病、肺部疾病、心脏代谢疾病和癌症。然而，人们对QCS之间的相互作用及其在这些疾病中的潜在作用了解甚少。在本综述中，我们概述了QCS及其相互作用的当前研究结果，涵盖线粒体、内质网、高尔基体、核糖体、过氧化物酶体、脂滴和溶酶体，以及这些细胞器之间异常的相互作用，这些相互作用导致了与衰老相关疾病的发生和发展。此外，还讨论了基于这些质量控制相互作用的潜在治疗方法。我们的观点可以增强对QCS潜在调控网络以及衰老和衰老相关疾病病理学的认识，这可能为开发新的治疗靶点铺平道路。
