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

Medini, Hadar; Zirman, Amit; Mo, Dan

doi:10.1016/j.isci.2021.103471

Cited by 31 publications

(40 citation statements)

References 58 publications

(66 reference statements)

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“…We observed in COVID19 positive cases, the blood mRNA levels for FOXRED1 (complex I assembly) and SCO2 (complex IV assembly) were up regulated ( Fig. S4A ) as we observed in complex I module MT-ND4 and in complex IV MT-CO2 module, SCO2 induction also being observed by others ( 17 ) ( Fig. S4B ).…”

Section: Resultssupporting

confidence: 81%

“…The reduction in CAT transcription is consistent with the virus inhibiting OXPHOS and antioxidant enzymes to increase mROS levels ( Fig. S4B )( 17 ). Finally, mRNA and protein levels were up regulated for nDNA replication ( TYMS, TK1, PAICS ), folate metabolism ( DHFR ), and stress response ( DDIT4 regulation of mTOR).…”

Section: Resultssupporting

confidence: 77%

“…For glycolysis in the heart, we observed the up regulation of lactate dehydrogenases A ( LDHA ) which converts pyruvate to lactate and favors glycolysis, but the down regulation of lactate dehydrogenase B ( LDHB ) which converts lactate to pyruvate and favors OXPHOS, a pattern also reported in peripheral blood ( 17 ). The glucose carriers ( SLC2A1 and SLC2A4 ) were down regulated as was the monocarboxylate carrier 1 ( SLC16A1 ), which transports lactate across the mitochondrial inner membrane.…”

Section: Resultsmentioning

confidence: 58%

“…mtDNA transcripts and mitochondrial RNA polymerase ( POLRMT ) have been reported to be down regulated in blood cells while interferon response genes were induced ( 17 ) with the mitochondrial IFI27 transcript being the most discriminatory factor in SARS-CoV-2 blood ( 38, 43 ). We observed in COVID19 positive cases, the blood mRNA levels for FOXRED1 (complex I assembly) and SCO2 (complex IV assembly) were up regulated ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…SARS-CoV-2 infected human peripheral blood mononuclear cells (PMBC) and CaCo-2 cells also increased transcription of the HIF-1α ( 12 ). SARS-CoV-2 infection of PBMCs showed down regulation of mtDNA transcripts, mitochondrial function, and increased glycolysis ( 17 ) in association with elevated mitokines, fibroblast growth factor 21 (FGF21)( 18 ) and growth differentiation factor 15 (GDF-15)( 19 ). Expression of FGF-21 and GDF-15 are increased when the mitochondrial unfolded protein response (UPR MT ) and the cytosolic unfolded protein response (UPR CT ) are activated causing an imbalance between the nDNA and mtDNA mitochondrial translation products ( 20 ).…”

Section: Sars-cov-2 Infection Modulates Mitochondrial Bioenergeticsmentioning

confidence: 99%

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Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection

Guarnieri

Dybas

Fazelinia

et al. 2022

Preprint

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Defects in mitochondrial oxidative phosphorylation (OXPHOS) have been reported in COVID-19 patients, but the timing and organs affected vary among reports. Here, we reveal the dynamics of COVID-19 through transcription profiles in nasopharyngeal and autopsy samples from patients and infected rodent models. While mitochondrial bioenergetics is repressed in the viral nasopharyngeal portal of entry, it is up regulated in autopsy lung tissues from deceased patients. In most disease stages and organs, discrete OXPHOS functions are blocked by the virus, and this is countered by the host broadly up regulating unblocked OXPHOS functions. No such rebound is seen in autopsy heart, results in severe repression of genes across all OXPHOS modules. Hence, targeted enhancement of mitochondrial gene expression may mitigate the pathogenesis of COVID-19.

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Section: Resultssupporting

confidence: 81%

Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Section: Sars-cov-2 Infection Modulates Mitochondrial Bioenergeticsmentioning

confidence: 99%

See 3 more Smart Citations

Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection

Guarnieri

Dybas

Fazelinia

et al. 2022

Preprint

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Persistence of neutrophil extracellular traps and anticardiolipin auto‐antibodies in post‐acute phase COVID‐19 patients

Pisareva

Badiou

Mihalovičová

et al. 2022

Journal of Medical Virology

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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COVID‐19 metabolism: Mechanisms and therapeutic targets

Wang

Cao

Zhang³

et al. 2022

MedComm

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS‐CoV‐2‐induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID‐19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS‐CoV‐2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID‐19 metabolism. SARS‐CoV‐2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS‐CoV‐2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID‐19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS‐CoV‐2‐induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID‐19 pandemic.

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

Cited by 31 publications

References 58 publications

Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection

Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection

Persistence of neutrophil extracellular traps and anticardiolipin auto‐antibodies in post‐acute phase COVID‐19 patients

COVID‐19 metabolism: Mechanisms and therapeutic targets

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