Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

Conformation-dependent recognition of mutant HTT proteins by selective autophagy

With the support by the National Natural Science Foundation of China,a study led by Prof.Lu Boxun(鲁伯埙)from Fudan University demonstrates that a toxic mutant HTT species is resistant to selective autophagy,revealing the fundamental mechanism of Huntington’s Disease.The study was published

Selective role of autophagy in neuronal function and neurodegenerative diseases

Proteostasis is critical for neuronal maintenance and survival, and its imbalance leads to neurodegeneration with the hallmark of protein misfolding and aggregation. Macroautophagy becomes a major route for the clearance of protein aggregates that are normally poor substrates for the proteasome, the other protein quality-control machinery. As a flux process, macroautophagy （hereafter referred to as autophagy） involves the formation of the autophagosome, a double-membrane vesicle for engulfing unwanted cellular components such as protein aggregates, and the fusion of autophagosomes with lysosomes that contain many potent proteases for final degradation.

Emerging roles of autophagy in metabolism and metabolic disorders

The global prevalence of metabolic disorders is an immediate threat to human health. Genetic features, environmental aspects and lifestyle changes are the major risk factors determining metabolic dysfunction in the body. Autophagy is a housekeeping stress-induced lysosomal degradation pathway, which recycles macromolecules and metabolites for new protein synthesis and energy production and regulates cellular homeostasis by clearance of damaged protein or organelles. Recently, a dramatically increasing number of literatures has shown that defects of the autophagic machinery is associated with dysfunction of multiple metabolic tissues including pancreatic β cells, liver, adipose tissue and muscle, and is implicated in metabolic disorders such as obesity and insulin resistance. Here in this review, we summarize the representative works on these topics and discuss the versatile roles of autophagy in the regulation of cellular metabolism and its possible implication in metabolic diseases.