Identification of active natural products that induce lysosomal biogenesis by lysosome-based screening and biological evaluation

Lysosomal biogenesis is an essential adaptive process by which lysosomes exert their function in maintaining cellular homeostasis. Defects in lysosomal enzymes and functions lead to lysosome-related diseases, including lysosomal storage diseases and neurodegenerative disorders. Thus, activation of t...

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Main Authors: Xiao Ding, Xu Yang, Yueqin Zhao, Yinyuan Wang, Jimin Fei, Zhenpeng Niu, Xianxiang Dong, Xuenan Wang, Biao Liu, Hongmei Li, Xiaojiang Hao, Yuhan Zhao
Format: Article
Language:English
Published: Elsevier 2022-10-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844022024677
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author Xiao Ding
Xu Yang
Yueqin Zhao
Yinyuan Wang
Jimin Fei
Zhenpeng Niu
Xianxiang Dong
Xuenan Wang
Biao Liu
Hongmei Li
Xiaojiang Hao
Yuhan Zhao
author_facet Xiao Ding
Xu Yang
Yueqin Zhao
Yinyuan Wang
Jimin Fei
Zhenpeng Niu
Xianxiang Dong
Xuenan Wang
Biao Liu
Hongmei Li
Xiaojiang Hao
Yuhan Zhao
author_sort Xiao Ding
collection DOAJ
description Lysosomal biogenesis is an essential adaptive process by which lysosomes exert their function in maintaining cellular homeostasis. Defects in lysosomal enzymes and functions lead to lysosome-related diseases, including lysosomal storage diseases and neurodegenerative disorders. Thus, activation of the autophagy-lysosomal pathway, especially induction of lysosomal biogenesis, might be an effective strategy for the treatment of lysosome-related diseases. In this study, we established a lysosome-based screening system to identify active compounds from natural products that could promote lysosomal biogenesis. The subcellular localizations of master transcriptional regulators of lysosomal genes, TFEB, TFE3 and ZKSCAN3 were examined to reveal the potential mechanisms. More than 200 compounds were screened, and we found that Hdj-23, a triterpene isolated from Walsura cochinchinensis, induced lysosomal biogenesis via activation of TFEB/TFE3. In summary, this study introduced a lysosome-based live cell screening strategy to identify bioactive compounds that promote lysosomal biogenesis, which would provide potential candidate enhancers of lysosomal biogenesis and novel insight for treating lysosome-related diseases.
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spelling doaj.art-3ce6f0511eed477b97e67f21591878172022-12-22T04:33:20ZengElsevierHeliyon2405-84402022-10-01810e11179Identification of active natural products that induce lysosomal biogenesis by lysosome-based screening and biological evaluationXiao Ding0Xu Yang1Yueqin Zhao2Yinyuan Wang3Jimin Fei4Zhenpeng Niu5Xianxiang Dong6Xuenan Wang7Biao Liu8Hongmei Li9Xiaojiang Hao10Yuhan Zhao11State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; Research Unit of Chemical Biology of Natural Anti-Virus Products, Chinese Academy of Medical Sciences, Beijing 100730, PR China; Corresponding author.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; School of Life Sciences, Yunnan University, Kunming 650091, Yunnan, PR ChinaYunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, Yunnan, PR ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; School of Basic Medicine, Guizhou Medical University, Guiyang 550009, Guizhou, PR ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, PR ChinaYunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, Yunnan, PR ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR ChinaState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; Research Unit of Chemical Biology of Natural Anti-Virus Products, Chinese Academy of Medical Sciences, Beijing 100730, PR China; Corresponding author.State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China; Corresponding author.Lysosomal biogenesis is an essential adaptive process by which lysosomes exert their function in maintaining cellular homeostasis. Defects in lysosomal enzymes and functions lead to lysosome-related diseases, including lysosomal storage diseases and neurodegenerative disorders. Thus, activation of the autophagy-lysosomal pathway, especially induction of lysosomal biogenesis, might be an effective strategy for the treatment of lysosome-related diseases. In this study, we established a lysosome-based screening system to identify active compounds from natural products that could promote lysosomal biogenesis. The subcellular localizations of master transcriptional regulators of lysosomal genes, TFEB, TFE3 and ZKSCAN3 were examined to reveal the potential mechanisms. More than 200 compounds were screened, and we found that Hdj-23, a triterpene isolated from Walsura cochinchinensis, induced lysosomal biogenesis via activation of TFEB/TFE3. In summary, this study introduced a lysosome-based live cell screening strategy to identify bioactive compounds that promote lysosomal biogenesis, which would provide potential candidate enhancers of lysosomal biogenesis and novel insight for treating lysosome-related diseases.http://www.sciencedirect.com/science/article/pii/S2405844022024677Lysosomal biogenesisNatural productsTFEB and TFE3Lysosome-based screeningAutophagy
spellingShingle Xiao Ding
Xu Yang
Yueqin Zhao
Yinyuan Wang
Jimin Fei
Zhenpeng Niu
Xianxiang Dong
Xuenan Wang
Biao Liu
Hongmei Li
Xiaojiang Hao
Yuhan Zhao
Identification of active natural products that induce lysosomal biogenesis by lysosome-based screening and biological evaluation
Heliyon
Lysosomal biogenesis
Natural products
TFEB and TFE3
Lysosome-based screening
Autophagy
title Identification of active natural products that induce lysosomal biogenesis by lysosome-based screening and biological evaluation
title_full Identification of active natural products that induce lysosomal biogenesis by lysosome-based screening and biological evaluation
title_fullStr Identification of active natural products that induce lysosomal biogenesis by lysosome-based screening and biological evaluation
title_full_unstemmed Identification of active natural products that induce lysosomal biogenesis by lysosome-based screening and biological evaluation
title_short Identification of active natural products that induce lysosomal biogenesis by lysosome-based screening and biological evaluation
title_sort identification of active natural products that induce lysosomal biogenesis by lysosome based screening and biological evaluation
topic Lysosomal biogenesis
Natural products
TFEB and TFE3
Lysosome-based screening
Autophagy
url http://www.sciencedirect.com/science/article/pii/S2405844022024677
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