Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou 510632, China.
Theranostics. 2021 Jan 1;11(1):222-256. doi: 10.7150/thno.49860. eCollection 2021.
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, . In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, . Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
自噬(以下简称自噬)是一种高度保守的生理过程,通过溶酶体系统(植物和酵母中的液泡)降解多余或受损的细胞器、大的蛋白质聚集体和入侵的病原体。自噬通常由应激诱导,如缺氧、能量或氨基酸剥夺、辐射、药物等。除了非选择性的批量降解外,自噬还以选择性方式发生,回收特定的细胞器,如线粒体、过氧化物酶体、核糖体、内质网(ER)、溶酶体、核、蛋白酶体和脂滴(LDs)。这种能力使选择性自噬成为维持细胞内稳态的主要过程。选择性自噬的功能障碍与神经退行性疾病(NDDs)、肿瘤发生、代谢紊乱、心力衰竭等有关。鉴于选择性自噬在细胞生物学中的重要性,我们系统地综述了近年来对这一过程及其调控机制的理解进展。我们强调了酵母和哺乳动物中特定细胞器或细胞成分的选择性自噬的“货物-配体-受体”模型,重点描述了线粒体自噬和 ER 自噬,它们被详细描述为选择性自噬的类型。此外,我们还强调了该领域未解决的问题,帮助读者关注需要突破的研究盲点。