文章基本信息

标题：Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
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作者：Hadar Medini ; Amit Zirman ; Dan Mishmar 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：12
页码：1-18
DOI：10.1016/j.isci.2021.103471
语种：English
出版社：Elsevier
摘要：SummaryMitochondria 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.Graphical abstractDisplay OmittedHighlights•mtDNA gene expression is downregulated in COVID-19 blood, but not in respiratory tract•Decreased mtDNA gene expression disrupts mito-nuclear coordination•mtDNA is downregulated and rewired toward glycolysis especially in immune system cells•Mitochondrial dysfunction is central to the etiology of COVID19Immune system; Virology; Genomics