Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis

Summary: Mitochondria are pivotal for bioenergetics, as well as in cellular response to viral infections. Nevertheless, their role in COVID-19 was largely overlooked. Here, we analyzed available bulk RNA-seq datasets from COVID-19 patients and corresponding healthy controls (three blood datasets, N ...

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Autores principales:	Hadar Medini, Amit Zirman, Dan Mishmar
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Immune system Virology Genomics Science Q
Acceso en línea:	https://doaj.org/article/54cb9f499310415dae8304ed758a5b28
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spelling	oai:doaj.org-article:54cb9f499310415dae8304ed758a5b282021-11-28T04:37:09ZImmune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis2589-004210.1016/j.isci.2021.103471https://doaj.org/article/54cb9f499310415dae8304ed758a5b282021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221014425https://doaj.org/toc/2589-0042Summary: Mitochondria are pivotal for bioenergetics, as well as in cellular response to viral infections. Nevertheless, their role in COVID-19 was largely overlooked. Here, we analyzed available bulk RNA-seq datasets from COVID-19 patients and corresponding healthy controls (three blood datasets, N = 48 healthy, 119 patients; two respiratory tract datasets, N = 157 healthy, 524 patients). We found significantly reduced mtDNA gene expression in blood, but not in respiratory tract samples from patients. Next, analysis of eight single-cells RNA-seq datasets from peripheral blood mononuclear cells, nasopharyngeal samples, and Bronchoalveolar lavage fluid (N = 1,192,243 cells), revealed significantly reduced mtDNA gene expression especially in immune system cells from patients. This is associated with elevated expression of nuclear DNA-encoded OXPHOS subunits, suggesting compromised mitochondrial-nuclear co-regulation. This, together with elevated expression of ROS-response genes and glycolysis enzymes in patients, suggest rewiring toward glycolysis, thus generating beneficial conditions for SARS-CoV-2 replication. Our findings underline the centrality of mitochondrial dysfunction in COVID-19.Hadar MediniAmit ZirmanDan MishmarElsevierarticleImmune systemVirologyGenomicsScienceQENiScience, Vol 24, Iss 12, Pp 103471- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immune system Virology Genomics Science Q
spellingShingle	Immune system Virology Genomics Science Q Hadar Medini Amit Zirman Dan Mishmar Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
description	Summary: Mitochondria are pivotal for bioenergetics, as well as in cellular response to viral infections. Nevertheless, their role in COVID-19 was largely overlooked. Here, we analyzed available bulk RNA-seq datasets from COVID-19 patients and corresponding healthy controls (three blood datasets, N = 48 healthy, 119 patients; two respiratory tract datasets, N = 157 healthy, 524 patients). We found significantly reduced mtDNA gene expression in blood, but not in respiratory tract samples from patients. Next, analysis of eight single-cells RNA-seq datasets from peripheral blood mononuclear cells, nasopharyngeal samples, and Bronchoalveolar lavage fluid (N = 1,192,243 cells), revealed significantly reduced mtDNA gene expression especially in immune system cells from patients. This is associated with elevated expression of nuclear DNA-encoded OXPHOS subunits, suggesting compromised mitochondrial-nuclear co-regulation. This, together with elevated expression of ROS-response genes and glycolysis enzymes in patients, suggest rewiring toward glycolysis, thus generating beneficial conditions for SARS-CoV-2 replication. Our findings underline the centrality of mitochondrial dysfunction in COVID-19.
format	article
author	Hadar Medini Amit Zirman Dan Mishmar
author_facet	Hadar Medini Amit Zirman Dan Mishmar
author_sort	Hadar Medini
title	Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
title_short	Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
title_full	Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
title_fullStr	Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
title_full_unstemmed	Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
title_sort	immune system cells from covid-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/54cb9f499310415dae8304ed758a5b28
work_keys_str_mv	AT hadarmedini immunesystemcellsfromcovid19patientsdisplaycompromisedmitochondrialnuclearexpressioncoregulationandrewiringtowardglycolysis AT amitzirman immunesystemcellsfromcovid19patientsdisplaycompromisedmitochondrialnuclearexpressioncoregulationandrewiringtowardglycolysis AT danmishmar immunesystemcellsfromcovid19patientsdisplaycompromisedmitochondrialnuclearexpressioncoregulationandrewiringtowardglycolysis
_version_	1718408258531622912

Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis

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