Cargando…

Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2

Thymidine kinase 2 (TK2) deficiency in humans leads to a myopathic form of mitochondrial DNA (mtDNA) deficiency. Here we present a skeletal and cardiac muscle specific TK2 knockout mouse (mTk2 KO). The mice showed dilated hearts and markedly reduced adipose tissue during week 12 to 16. A severe decr...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Qian, Zhou, Xiaoshan, Kuiper, Raoul, Curbo, Sophie, Karlsson, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242481/
https://www.ncbi.nlm.nih.gov/pubmed/35767531
http://dx.doi.org/10.1371/journal.pone.0270418
_version_ 1784738068747517952
author Zhao, Qian
Zhou, Xiaoshan
Kuiper, Raoul
Curbo, Sophie
Karlsson, Anna
author_facet Zhao, Qian
Zhou, Xiaoshan
Kuiper, Raoul
Curbo, Sophie
Karlsson, Anna
author_sort Zhao, Qian
collection PubMed
description Thymidine kinase 2 (TK2) deficiency in humans leads to a myopathic form of mitochondrial DNA (mtDNA) deficiency. Here we present a skeletal and cardiac muscle specific TK2 knockout mouse (mTk2 KO). The mice showed dilated hearts and markedly reduced adipose tissue during week 12 to 16. A severe decrease of mtDNA was found only in skeletal muscle and heart tissue in mTk2 KO mice. Expression analysis of key metabolic genes of 16 weeks knockout mice showed significant changes of genes involved in lipid metabolism, with different patterns in heart and skeletal muscle. Our study further suggests that lipoprotein lipase (LPL) from liver supports the metabolism when heart and skeletal muscle were impaired due to mitochondrial dysfunction. The angiotensin-converting enzyme 2 (ACE2), which is involved in glucose homeostasis, was also affected by mtDNA deficiency in our study. Interestingly, both the gene and protein expression of ACE2 were increased in cardiac tissue of mTk2 KO mice. Since ACE2 is a receptor for the SARS-CoV-2 virus, its regulation in relation to mitochondrial function may have important clinical implications.
format Online
Article
Text
id pubmed-9242481
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-92424812022-06-30 Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2 Zhao, Qian Zhou, Xiaoshan Kuiper, Raoul Curbo, Sophie Karlsson, Anna PLoS One Research Article Thymidine kinase 2 (TK2) deficiency in humans leads to a myopathic form of mitochondrial DNA (mtDNA) deficiency. Here we present a skeletal and cardiac muscle specific TK2 knockout mouse (mTk2 KO). The mice showed dilated hearts and markedly reduced adipose tissue during week 12 to 16. A severe decrease of mtDNA was found only in skeletal muscle and heart tissue in mTk2 KO mice. Expression analysis of key metabolic genes of 16 weeks knockout mice showed significant changes of genes involved in lipid metabolism, with different patterns in heart and skeletal muscle. Our study further suggests that lipoprotein lipase (LPL) from liver supports the metabolism when heart and skeletal muscle were impaired due to mitochondrial dysfunction. The angiotensin-converting enzyme 2 (ACE2), which is involved in glucose homeostasis, was also affected by mtDNA deficiency in our study. Interestingly, both the gene and protein expression of ACE2 were increased in cardiac tissue of mTk2 KO mice. Since ACE2 is a receptor for the SARS-CoV-2 virus, its regulation in relation to mitochondrial function may have important clinical implications. Public Library of Science 2022-06-29 /pmc/articles/PMC9242481/ /pubmed/35767531 http://dx.doi.org/10.1371/journal.pone.0270418 Text en © 2022 Zhao et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhao, Qian
Zhou, Xiaoshan
Kuiper, Raoul
Curbo, Sophie
Karlsson, Anna
Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2
title Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2
title_full Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2
title_fullStr Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2
title_full_unstemmed Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2
title_short Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2
title_sort mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242481/
https://www.ncbi.nlm.nih.gov/pubmed/35767531
http://dx.doi.org/10.1371/journal.pone.0270418
work_keys_str_mv AT zhaoqian mitochondrialdysfunctionisassociatedwithlipidmetabolismdisorderandupregulationofangiotensinconvertingenzyme2
AT zhouxiaoshan mitochondrialdysfunctionisassociatedwithlipidmetabolismdisorderandupregulationofangiotensinconvertingenzyme2
AT kuiperraoul mitochondrialdysfunctionisassociatedwithlipidmetabolismdisorderandupregulationofangiotensinconvertingenzyme2
AT curbosophie mitochondrialdysfunctionisassociatedwithlipidmetabolismdisorderandupregulationofangiotensinconvertingenzyme2
AT karlssonanna mitochondrialdysfunctionisassociatedwithlipidmetabolismdisorderandupregulationofangiotensinconvertingenzyme2