Loss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons

Abstract Succinyl Coenzyme A synthetase (SCS) is a key mitochondrial enzyme. Defected SCS ADP-forming β subunit (SCS A-β) is linked to lethal infantile Leigh or leigh-like syndrome. However, the impacts of SCS A-β deficiency on mitochondria specifically in neurons have not yet been comprehensively i...

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Autores principales:	Yujun Zhao, Jing Tian, Shaomei Sui, Xiaodong Yuan, Hao Chen, Chuanqiang Qu, Yifeng Du, Lan Guo, Heng Du
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f4d68f35beb4d518f4f69fc1f40df70
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spelling	oai:doaj.org-article:5f4d68f35beb4d518f4f69fc1f40df702021-12-02T16:06:22ZLoss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons10.1038/s41598-017-05168-52045-2322https://doaj.org/article/5f4d68f35beb4d518f4f69fc1f40df702017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05168-5https://doaj.org/toc/2045-2322Abstract Succinyl Coenzyme A synthetase (SCS) is a key mitochondrial enzyme. Defected SCS ADP-forming β subunit (SCS A-β) is linked to lethal infantile Leigh or leigh-like syndrome. However, the impacts of SCS A-β deficiency on mitochondria specifically in neurons have not yet been comprehensively investigated. Here, by down-regulating the expression levels of SCS A-β in cultured mouse neurons, we have found that SCS A-β deficiency induces severe mitochondrial dysfunction including lowered oxidative phosphorylation (OXPHOS) efficiency, increased mitochondrial superoxide production, and mtDNA depletion as well as aberrations of mitochondrial fusion and fission proteins, which eventually leads to neuronal stress. Our data also suggest that the deregulation of mitochondrial nucleoside diphosphate kinase (NDPK) together with defects in mitochondrial transcription factors including mitochondrial DNA pol γ and Twinkle contribute to SCS A-β deficiency-mediated mtDNA instability. Furthermore, we have found that SCS A-β deficiency has detrimental influence on neuronal mitochondrial dynamics. Put together, the results have furnished our knowledge on the pathogenesis of SCS A-β deficiency-related mitochondrial diseases and revealed the vital role of SCS A-β in maintaining neuronal mitochondrial quality control and neuronal physiology.Yujun ZhaoJing TianShaomei SuiXiaodong YuanHao ChenChuanqiang QuYifeng DuLan GuoHeng DuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yujun Zhao Jing Tian Shaomei Sui Xiaodong Yuan Hao Chen Chuanqiang Qu Yifeng Du Lan Guo Heng Du Loss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons
description	Abstract Succinyl Coenzyme A synthetase (SCS) is a key mitochondrial enzyme. Defected SCS ADP-forming β subunit (SCS A-β) is linked to lethal infantile Leigh or leigh-like syndrome. However, the impacts of SCS A-β deficiency on mitochondria specifically in neurons have not yet been comprehensively investigated. Here, by down-regulating the expression levels of SCS A-β in cultured mouse neurons, we have found that SCS A-β deficiency induces severe mitochondrial dysfunction including lowered oxidative phosphorylation (OXPHOS) efficiency, increased mitochondrial superoxide production, and mtDNA depletion as well as aberrations of mitochondrial fusion and fission proteins, which eventually leads to neuronal stress. Our data also suggest that the deregulation of mitochondrial nucleoside diphosphate kinase (NDPK) together with defects in mitochondrial transcription factors including mitochondrial DNA pol γ and Twinkle contribute to SCS A-β deficiency-mediated mtDNA instability. Furthermore, we have found that SCS A-β deficiency has detrimental influence on neuronal mitochondrial dynamics. Put together, the results have furnished our knowledge on the pathogenesis of SCS A-β deficiency-related mitochondrial diseases and revealed the vital role of SCS A-β in maintaining neuronal mitochondrial quality control and neuronal physiology.
format	article
author	Yujun Zhao Jing Tian Shaomei Sui Xiaodong Yuan Hao Chen Chuanqiang Qu Yifeng Du Lan Guo Heng Du
author_facet	Yujun Zhao Jing Tian Shaomei Sui Xiaodong Yuan Hao Chen Chuanqiang Qu Yifeng Du Lan Guo Heng Du
author_sort	Yujun Zhao
title	Loss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons
title_short	Loss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons
title_full	Loss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons
title_fullStr	Loss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons
title_full_unstemmed	Loss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons
title_sort	loss of succinyl-coa synthase adp-forming β subunit disrupts mtdna stability and mitochondrial dynamics in neurons
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5f4d68f35beb4d518f4f69fc1f40df70
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Loss of succinyl-CoA synthase ADP-forming β subunit disrupts mtDNA stability and mitochondrial dynamics in neurons

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