Optogenetic control of mitochondrial aggregation and function

The balance of mitochondrial fission and fusion plays an important role in maintaining the stability of cellular homeostasis. Abnormal mitochondrial fission and fragmentation have been shown to be associated with oxidative stress, which causes a variety of human diseases from neurodegeneration disea...

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Main Authors: Luhao Zhang, Xuechun Liu, Min Zhu, Yuanfa Yao, Zhichao Liu, Xianming Zhang, Xin Deng, Yi Wang, Liting Duan, Xiaogang Guo, Junfen Fu, Yingke Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Bioengineering and Biotechnology
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Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2024.1500343/full
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author Luhao Zhang
Luhao Zhang
Luhao Zhang
Xuechun Liu
Min Zhu
Min Zhu
Yuanfa Yao
Zhichao Liu
Xianming Zhang
Xin Deng
Yi Wang
Liting Duan
Xiaogang Guo
Junfen Fu
Yingke Xu
Yingke Xu
Yingke Xu
author_facet Luhao Zhang
Luhao Zhang
Luhao Zhang
Xuechun Liu
Min Zhu
Min Zhu
Yuanfa Yao
Zhichao Liu
Xianming Zhang
Xin Deng
Yi Wang
Liting Duan
Xiaogang Guo
Junfen Fu
Yingke Xu
Yingke Xu
Yingke Xu
author_sort Luhao Zhang
collection DOAJ
description The balance of mitochondrial fission and fusion plays an important role in maintaining the stability of cellular homeostasis. Abnormal mitochondrial fission and fragmentation have been shown to be associated with oxidative stress, which causes a variety of human diseases from neurodegeneration disease to cancer. Therefore, the induction of mitochondrial aggregation and fusion may provide an alternative approach to alleviate these conditions. Here, an optogenetic-based mitochondrial aggregation system (Opto-MitoA) developed, which is based on the CRY2clust/CIBN light-sensitive module. Upon blue light illumination, CRY2clust relocates from the cytosol to mitochondria where it induces mitochondrial aggregation by CRY2clust homo-oligomerization and CRY2clust-CIBN hetero-dimerization. Our functional experiments demonstrate that Opto-MitoA-induced mitochondrial aggregation potently alleviates niclosamide-caused cell dysfunction in ATP production. This study establishes a novel optogenetic-based strategy to regulate mitochondrial dynamics in cells, which may provide a potential therapy for treating mitochondrial-related diseases.
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publishDate 2025-01-01
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series Frontiers in Bioengineering and Biotechnology
spelling doaj-art-90249608858d4c3f8b0355dab6cd76842025-01-06T06:59:45ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-01-011210.3389/fbioe.2024.15003431500343Optogenetic control of mitochondrial aggregation and functionLuhao Zhang0Luhao Zhang1Luhao Zhang2Xuechun Liu3Min Zhu4Min Zhu5Yuanfa Yao6Zhichao Liu7Xianming Zhang8Xin Deng9Yi Wang10Liting Duan11Xiaogang Guo12Junfen Fu13Yingke Xu14Yingke Xu15Yingke Xu16Department of Endocrinology, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Children’s Health, Hangzhou, ChinaDepartment of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, ChinaInnovation Center for Smart Medical Technologies and Devices, Binjiang Institute of Zhejiang University, Hangzhou, ChinaDepartment of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, ChinaDepartment of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, ChinaDepartment of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, ChinaDepartment of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, ChinaDepartment of Endocrinology, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Children’s Health, Hangzhou, ChinaPharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaDepartment of Biomedical Engineering, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, ChinaDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Endocrinology, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Children’s Health, Hangzhou, ChinaDepartment of Endocrinology, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Children’s Health, Hangzhou, ChinaDepartment of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, ChinaInnovation Center for Smart Medical Technologies and Devices, Binjiang Institute of Zhejiang University, Hangzhou, ChinaThe balance of mitochondrial fission and fusion plays an important role in maintaining the stability of cellular homeostasis. Abnormal mitochondrial fission and fragmentation have been shown to be associated with oxidative stress, which causes a variety of human diseases from neurodegeneration disease to cancer. Therefore, the induction of mitochondrial aggregation and fusion may provide an alternative approach to alleviate these conditions. Here, an optogenetic-based mitochondrial aggregation system (Opto-MitoA) developed, which is based on the CRY2clust/CIBN light-sensitive module. Upon blue light illumination, CRY2clust relocates from the cytosol to mitochondria where it induces mitochondrial aggregation by CRY2clust homo-oligomerization and CRY2clust-CIBN hetero-dimerization. Our functional experiments demonstrate that Opto-MitoA-induced mitochondrial aggregation potently alleviates niclosamide-caused cell dysfunction in ATP production. This study establishes a novel optogenetic-based strategy to regulate mitochondrial dynamics in cells, which may provide a potential therapy for treating mitochondrial-related diseases.https://www.frontiersin.org/articles/10.3389/fbioe.2024.1500343/fulloptogeneticsmitochondriaaggregationATPimaging
spellingShingle Luhao Zhang
Luhao Zhang
Luhao Zhang
Xuechun Liu
Min Zhu
Min Zhu
Yuanfa Yao
Zhichao Liu
Xianming Zhang
Xin Deng
Yi Wang
Liting Duan
Xiaogang Guo
Junfen Fu
Yingke Xu
Yingke Xu
Yingke Xu
Optogenetic control of mitochondrial aggregation and function
Frontiers in Bioengineering and Biotechnology
optogenetics
mitochondria
aggregation
ATP
imaging
title Optogenetic control of mitochondrial aggregation and function
title_full Optogenetic control of mitochondrial aggregation and function
title_fullStr Optogenetic control of mitochondrial aggregation and function
title_full_unstemmed Optogenetic control of mitochondrial aggregation and function
title_short Optogenetic control of mitochondrial aggregation and function
title_sort optogenetic control of mitochondrial aggregation and function
topic optogenetics
mitochondria
aggregation
ATP
imaging
url https://www.frontiersin.org/articles/10.3389/fbioe.2024.1500343/full
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