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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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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 |
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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 |
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