Peroxisomes and pexophagy have gained increasing attention in their role within the central nervous system(CNS)in recent years.In this review,we comprehensively discussed the physiological and pathological mech-anisms...Peroxisomes and pexophagy have gained increasing attention in their role within the central nervous system(CNS)in recent years.In this review,we comprehensively discussed the physiological and pathological mech-anisms of peroxisomes and pexophagy in neurological diseases.Peroxisomes communicate with mitochondria,endoplasmic reticulum,and lipid bodies.Their types,sizes,and shapes vary in different regions of the brain.Moreover,peroxisomes play an important role in oxidative homeostasis,lipid synthesis,and degradation in the CNS,whereas its dysfunction causes various neurological diseases.Therefore,selective removal of dysfunctional or superfluous peroxisomes(pexophagy)provides neuroprotective effects,which indicate a promising therapeu-tic target.However,pexophagy largely remains unexplored in neurological disorders.More studies are needed to explore the pexophagy’s crosstalk mechanisms in neurological pathology.展开更多
Protein ubiquitination regulates diverse cellular processes in eukaryotic organisms,from growth and development to stress response.Proteins subjected to ubiquitination can be found in virtually all subcellular locatio...Protein ubiquitination regulates diverse cellular processes in eukaryotic organisms,from growth and development to stress response.Proteins subjected to ubiquitination can be found in virtually all subcellular locations and organelles,including peroxisomes,singlemembrane and highly dynamic organelles ubiquitous in eukaryotes.Peroxisomes contain metabolic functions essential to plants and animals such as lipid catabolism,detoxification of reactive oxygen species(ROS),biosynthesis of vital hormones and cofactors,and photorespiration.Plant peroxisomes possess a complex proteome with functions varying among different tissue types and developmental stages,and during plant response to distinct environmental cues.However,how these diverse functions are regulated at the post-translational level is poorly understood,especially in plants.In this review,we summarized current knowledge of the involvement of protein ubiquitination in peroxisome protein import,remodeling,pexophagy,and metabolism,focusing on plants,and referencing discoveries from other eukaryotic systems when relevant.Based on previous ubiquitinomics studies,we compiled a list of 56 ubiquitinated Arabidopsis peroxisomal proteins whose functions are associated with all the major plant peroxisomal metabolic pathways.This discovery suggests a broad impact of protein ubiquitination on plant peroxisome functions,therefore substantiating the need to investigate this significant regulatory mechanism in peroxisomes at more depths.展开更多
基金supported by the National Institutes of Health(NS084921,NS082184,and NS43338)National Natural Science Foundation of China(82001231,82001299)+1 种基金Zhejiang Provincial Natural Science Foundation of China(LQ21H090009)Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China under Grant(LHDMZ22H300014).
文摘Peroxisomes and pexophagy have gained increasing attention in their role within the central nervous system(CNS)in recent years.In this review,we comprehensively discussed the physiological and pathological mech-anisms of peroxisomes and pexophagy in neurological diseases.Peroxisomes communicate with mitochondria,endoplasmic reticulum,and lipid bodies.Their types,sizes,and shapes vary in different regions of the brain.Moreover,peroxisomes play an important role in oxidative homeostasis,lipid synthesis,and degradation in the CNS,whereas its dysfunction causes various neurological diseases.Therefore,selective removal of dysfunctional or superfluous peroxisomes(pexophagy)provides neuroprotective effects,which indicate a promising therapeu-tic target.However,pexophagy largely remains unexplored in neurological disorders.More studies are needed to explore the pexophagy’s crosstalk mechanisms in neurological pathology.
基金supported by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2019R01002)Key Research Project of Zhejiang Laboratory(No.2021PE0AC04)+3 种基金Scientific Research Fund of Zhejiang Provincial Education Department(No.Y202148338)Zhejiang University Student Research Practice Program(No.P2021041)to R.P.by the National Science Foundation(No.MCB 2148206)US Department of Energy(No.DEFG02-91ER20021)to J.H。
文摘Protein ubiquitination regulates diverse cellular processes in eukaryotic organisms,from growth and development to stress response.Proteins subjected to ubiquitination can be found in virtually all subcellular locations and organelles,including peroxisomes,singlemembrane and highly dynamic organelles ubiquitous in eukaryotes.Peroxisomes contain metabolic functions essential to plants and animals such as lipid catabolism,detoxification of reactive oxygen species(ROS),biosynthesis of vital hormones and cofactors,and photorespiration.Plant peroxisomes possess a complex proteome with functions varying among different tissue types and developmental stages,and during plant response to distinct environmental cues.However,how these diverse functions are regulated at the post-translational level is poorly understood,especially in plants.In this review,we summarized current knowledge of the involvement of protein ubiquitination in peroxisome protein import,remodeling,pexophagy,and metabolism,focusing on plants,and referencing discoveries from other eukaryotic systems when relevant.Based on previous ubiquitinomics studies,we compiled a list of 56 ubiquitinated Arabidopsis peroxisomal proteins whose functions are associated with all the major plant peroxisomal metabolic pathways.This discovery suggests a broad impact of protein ubiquitination on plant peroxisome functions,therefore substantiating the need to investigate this significant regulatory mechanism in peroxisomes at more depths.
