Immune system cells from COVID-19 patients display compromised mitochondrial-nuclear expression co-regulation and rewiring toward glycolysis
| Autor: | Amit Zirman, Hadar Medini, Dan Mishmar |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | iScience, Vol 24, Iss 12, Pp 103471-(2021) iScience |
| ISSN: | 2589-0042 |
| Popis: | 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. Graphical abstract Immune system; Virology; Genomics |
| Databáze: | OpenAIRE |
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