Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia

Abstract Biliary atresia (BA) results in severe bile blockage and is caused by the absence of extrahepatic ducts. Even after successful hepatic portoenterostomy, a considerable number of patients are likely to show progressive deterioration in liver function. Recent studies show that mutations in pr...

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Autores principales:	Hong Koh, Gun-Seok Park, Sun-Mi Shin, Chang Eon Park, Seung Kim, Seok Joo Han, Huy Quang Pham, Jae-Ho Shin, Dong-Woo Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e0e5ff8734534cf2925a73a8db5a2517
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spelling	oai:doaj.org-article:e0e5ff8734534cf2925a73a8db5a25172021-12-02T15:08:28ZMitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia10.1038/s41598-017-18958-82045-2322https://doaj.org/article/e0e5ff8734534cf2925a73a8db5a25172018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-18958-8https://doaj.org/toc/2045-2322Abstract Biliary atresia (BA) results in severe bile blockage and is caused by the absence of extrahepatic ducts. Even after successful hepatic portoenterostomy, a considerable number of patients are likely to show progressive deterioration in liver function. Recent studies show that mutations in protein-coding mitochondrial DNA (mtDNA) genes and/or mitochondrial genes in nuclear DNA (nDNA) are associated with hepatocellular dysfunction. This observation led us to investigate whether hepatic dysfunctions in BA is genetically associated with mtDNA mutations. We sequenced the mtDNA protein-coding genes in 14 liver specimens from 14 patients with BA and 5 liver specimens from 5 patients with choledochal cyst using next-generation sequencing. We found 34 common non-synonymous variations in mtDNA protein-coding genes in all patients examined. A systematic 3D structural analysis revealed the presence of several single nucleotide polymorphism-like mutations in critical regions of complexes I to V, that are involved in subunit assembly, proton-pumping activity, and/or supercomplex formation. The parameters of chronic hepatic injury and liver dysfunction in BA patients were also significantly correlated with the extent of hepatic failure, suggesting that the mtDNA mutations may aggravate hepatopathy. Therefore, mitochondrial mutations may underlie the pathological mechanisms associated with BA.Hong KohGun-Seok ParkSun-Mi ShinChang Eon ParkSeung KimSeok Joo HanHuy Quang PhamJae-Ho ShinDong-Woo LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hong Koh Gun-Seok Park Sun-Mi Shin Chang Eon Park Seung Kim Seok Joo Han Huy Quang Pham Jae-Ho Shin Dong-Woo Lee Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia
description	Abstract Biliary atresia (BA) results in severe bile blockage and is caused by the absence of extrahepatic ducts. Even after successful hepatic portoenterostomy, a considerable number of patients are likely to show progressive deterioration in liver function. Recent studies show that mutations in protein-coding mitochondrial DNA (mtDNA) genes and/or mitochondrial genes in nuclear DNA (nDNA) are associated with hepatocellular dysfunction. This observation led us to investigate whether hepatic dysfunctions in BA is genetically associated with mtDNA mutations. We sequenced the mtDNA protein-coding genes in 14 liver specimens from 14 patients with BA and 5 liver specimens from 5 patients with choledochal cyst using next-generation sequencing. We found 34 common non-synonymous variations in mtDNA protein-coding genes in all patients examined. A systematic 3D structural analysis revealed the presence of several single nucleotide polymorphism-like mutations in critical regions of complexes I to V, that are involved in subunit assembly, proton-pumping activity, and/or supercomplex formation. The parameters of chronic hepatic injury and liver dysfunction in BA patients were also significantly correlated with the extent of hepatic failure, suggesting that the mtDNA mutations may aggravate hepatopathy. Therefore, mitochondrial mutations may underlie the pathological mechanisms associated with BA.
format	article
author	Hong Koh Gun-Seok Park Sun-Mi Shin Chang Eon Park Seung Kim Seok Joo Han Huy Quang Pham Jae-Ho Shin Dong-Woo Lee
author_facet	Hong Koh Gun-Seok Park Sun-Mi Shin Chang Eon Park Seung Kim Seok Joo Han Huy Quang Pham Jae-Ho Shin Dong-Woo Lee
author_sort	Hong Koh
title	Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia
title_short	Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia
title_full	Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia
title_fullStr	Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia
title_full_unstemmed	Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia
title_sort	mitochondrial mutations in cholestatic liver disease with biliary atresia
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e0e5ff8734534cf2925a73a8db5a2517
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Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia

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