The Mitochondrial Fission Regulator DRP1 Controls Post-Transcriptional Regulation of TNF-α DOI Creative Commons

Fushan Gao,

Mack B. Reynolds, Karla D. Passalacqua

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2021, Номер 10

Опубликована: Янв. 14, 2021

The mitochondrial network plays a critical role in the regulation of innate immune signaling and subsequent production proinflammatory cytokines such as IFN-β IL-1β. Dynamin-related protein 1 (DRP1) promotes fission quality control to maintain cellular homeostasis during infection. However, mechanisms by which DRP1 dynamics response are incompletely understood. Here we show that macrophage is positive regulator TNF-α sterile inflammation or bacterial Silencing decreased fragmentation upon stimulation with lipopolysaccharide (LPS) methicillin-resistant Staphylococcus aureus (MRSA) defect induction could not be attributed changes gene expression. Instead, was required for post-transcriptional TNF-α. In contrast, silencing enhanced IL-6 IL-1β production, indicating distinct mechanism DRP1-dependent regulation. Our results highlight key player pro-inflammatory point its involvement production.

Язык: Английский

Newcastle Disease Virus Manipulates Mitochondrial MTHFD2-Mediated Nucleotide Metabolism for Virus Replication DOI
Ning Tang,

Pingyi Chen,

Changrun Zhao

и другие.

Journal of Virology, Год журнала: 2023, Номер 97(3)

Опубликована: Фев. 16, 2023

Viruses require host cell metabolic reprogramming to satisfy their replication demands; however, the mechanism by which Newcastle disease virus (NDV) remodels nucleotide metabolism support self-replication remains unknown. In this study, we demonstrate that NDV relies on oxidative pentose phosphate pathway (oxPPP) and folate-mediated one-carbon replication. concert with [1,2-13C2] glucose flow, used oxPPP promote synthesis increase antioxidant NADPH production. Metabolic flux experiments using [2,3,3-2H] serine revealed increased (1C) unit through mitochondrial 1C pathway. Interestingly, methylenetetrahydrofolate dehydrogenase (MTHFD2) was upregulated as a compensatory for insufficient availability. Unexpectedly, direct knockdown of enzymes in pathway, except cytosolic MTHFD1, significantly inhibited Specific complementation rescue small interfering RNA (siRNA)-mediated further only MTHFD2 strongly restrained rescued formate extracellular nucleotides. These findings indicated maintain Notably, nuclear expression during infection could represent steals nucleotides from nucleus. Collectively, these data reveal is regulated c-Myc-mediated viral MTHFD2. IMPORTANCE dominant vector vaccine gene therapy accommodates foreign genes well but can infect mammalian cells have undergone cancerous transformation. Understanding remodeling pathways proliferation provides new perspective precise use or antiviral research. demonstrated strictly dependent involved redox homeostasis including Further investigation potential involvement replication-dependent availability promoting localization. Our highlight differential dependence metabolism, unique action replication, thereby providing novel target oncolytic therapy.

Язык: Английский

Процитировано

14
Metabolic reprogramming as a feast for virus replication DOI Open Access

Katarína Polčicová,

Lucia Baďurová,

Jana Tomášková

и другие.

Acta Virologica, Год журнала: 2020, Номер 64(02), С. 201 - 215

Опубликована: Янв. 1, 2020

Viral replication depends entirely on the energy and biosynthetic precursors supplied by host cell metabolic network. Viruses actively reprogram metabolism to establish optimal environment for their spread. They stimulate uptake of extracellular nutrients predominantly modulate glucose, glutamine, fatty acid support anabolic pathways. Some viruses activate process aerobic glycolysis, divert glycolytic carbon reactions, glutamine utilization replenish tricarboxylic cycle intermediates. Others use promote de novo synthesis, amino supply or glutathione production. The unique signature different dependence viral life individual processes is therefore characteristic feature almost each virus. Deeper understanding how alter cellular pathways upstream regulatory circuits may lead development more effective antiviral treatment strategies based targeted inhibition. Keywords: virus infection; metabolism; glycolysis; synthesis; reprogramming; virus-host interaction.

Язык: Английский

Процитировано

39
Oxygen: viral friend or foe? DOI Creative Commons
Esther S. Gan, Eng Eong Ooi

Virology Journal, Год журнала: 2020, Номер 17(1)

Опубликована: Июль 27, 2020

The oxygen levels organ and tissue microenvironments vary depending on the distance of their vasculature from left ventricle heart. For instance, lymph nodes spleen are significantly lower than that in atmospheric air. Cellular detection response to low can exert a significant impact virus infection. Generally, viruses naturally infect well-oxygenated organs less able cells under hypoxic conditions. Conversely, tensions thrive This suggests vitro experiments performed exclusively conditions ignores oxygen-induced modifications both host viral responses. Here, we review mechanisms how adapt its infections. With growing evidence supporting role infections, this highlights importance factoring concentrations into assay Bridging gap between vivo would allow for more physiologically representative insights pathogenesis.

Язык: Английский

Процитировано

36
A combinatorial approach of a polypharmacological adjuvant 2-deoxy-D-glucose with low dose radiation therapy to quell the cytokine storm in COVID-19 management DOI
Amit Verma, Amitava Adhikary, Gayle E. Woloschak

и другие.

International Journal of Radiation Biology, Год журнала: 2020, Номер 96(11), С. 1323 - 1328

Опубликована: Сен. 10, 2020

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic disease and the major cause of deaths worldwide. The clinical complexities (inflammation, cytokine storm, multi-organ dysfunction) associated with COVID-19 poses constraints to effective management critically ill patients. Low dose radiation therapy (LDRT) has been evaluated as potential therapeutic modality for pneumonia. However, due heterogeneity in manifestation inter-individual variations, planning LDRT limited this large-scale event. 2-deoxy-D-glucose (2-DG) emerged polypharmacological agent treatment its effects on glycolytic pathway, anti-inflammatory action, interaction viral proteins. We suggest that 2-DG will be adjuvant enhance efficacy Withal, azido analog 2-DG, 2-azido-2-DG can produce rapid catastrophic oxidative stress quell storm

Язык: Английский

Процитировано

34
The Mitochondrial Fission Regulator DRP1 Controls Post-Transcriptional Regulation of TNF-α DOI Creative Commons

Fushan Gao,

Mack B. Reynolds, Karla D. Passalacqua

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2021, Номер 10

Опубликована: Янв. 14, 2021

The mitochondrial network plays a critical role in the regulation of innate immune signaling and subsequent production proinflammatory cytokines such as IFN-β IL-1β. Dynamin-related protein 1 (DRP1) promotes fission quality control to maintain cellular homeostasis during infection. However, mechanisms by which DRP1 dynamics response are incompletely understood. Here we show that macrophage is positive regulator TNF-α sterile inflammation or bacterial Silencing decreased fragmentation upon stimulation with lipopolysaccharide (LPS) methicillin-resistant Staphylococcus aureus (MRSA) defect induction could not be attributed changes gene expression. Instead, was required for post-transcriptional TNF-α. In contrast, silencing enhanced IL-6 IL-1β production, indicating distinct mechanism DRP1-dependent regulation. Our results highlight key player pro-inflammatory point its involvement production.

Язык: Английский

Процитировано

24