Characterization the disruption of mitochondrial function and induction of oxidative stress by SARS-CoV2

SARS-CoV2 对线粒体功能的破坏和氧化应激诱导的表征

基本信息

  • 批准号:
    10640165
  • 负责人:
  • 金额:
    $ 23.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-06-08 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

1 Populations at higher risk of severe disease from COVID-19 are the elderly and those with metabolic 2 syndromes, the populations known for compromised mitochondrial function. In addition, the most common 3 symptoms in hospitalized COVID patients are shortness of breath and fatigue, indicating deficient oxygen and 4 energy metabolism, also suggesting defective mitochondria. COVID-19 patients also have significantly 5 elevated serum lactate dehydrogenase and increases oxidative stress, pointing to a possibility of reduced 6 mitochondrial oxidative phosphorylation (OXPHOS). Together, these information leads us to consider whether 7 mitochondrial dysfunction might contribute to the pathogenesis of COVID-19. A comprehensive proteomics 8 investigation and other studies identified at least 6 mitochondrially-localized SARS-CoV-2 viral proteins which 9 were shown to interact with host cell mitochondrial proteins involved in critical OXPHOS pathways converging 10 on respiratory Complex I biogenesis. Our lab has established expertise on the investigation of mitochondrial 11 biology and mitochondrial medicine, especially on Complex I-related OXPHOS biogenesis. Over the years we 12 have developed a series of unique cell models with different types of complex I defects, including sets of cells 13 with different contents of functional complex I subunits, a set cells with different complex I assembly capacity, 14 and a set of cells carrying pathogenic mutations in complex I subunit genes, as well as an engineered system 15 to rescue complex I-related function with the introduction of a yeast Complex I counterpart NDI1 gene. These 16 models exhibit different levels of complex I subunit expression, different capacities of complex I and overall 17 respiratory machinery assembly, and different complex I and overall mitochondrial OXPHOS activities. 18 Accordingly, these cell models also exhibit different sensitivities to oxidative stress and cell death. We have 19 also initiated a line of study on the effect of viruses on mitochondria and consequent implications on human 20 diseases. In addition, we have achieved to obtain 1.Inducible expression which could turn on and off the 21 SARS-CoV-2 proteins in our cell models at proper levels; 2.Multiple genes expression which can express 22 multiple SARS-CoV-2 proteins targeting one or multiple OXPHOS pathways simultaneously in our cell models; 23 3.Establishment of A549-hACE2 cell, where a human alveolar epithelial cell line, A549 was transduced with 24 lentiviruses expressing human ACE2. A549-hACE2 cells readily support SARS-CoV2 infection and replication; 25 4.Generated mutant SARS-CoV2 lines which could serve as controls. These provide a unique opportunity for 26 us to utilize our unique systems and expertise to fulfill with two independent and integrated aims to study the 27 interactions between SARS-CoV2 and mitochondria, and their implications on oxidative stress and cell death, 28 both in cell models with regulated mitochondrial function and in human alveolar epithelial cell line infected with 29 SARS-CoV2. We expect these research will help identify molecular targets of SARS-CoV2 proteins in host 30 cells and will also provide novel approaches for protecting against the harmful effects of COVID-19. 31 32
1 .老年人和代谢性疾病患者是COVID-19重症风险较高的人群

项目成果

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Yidong Bai其他文献

Yidong Bai的其他文献

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{{ truncateString('Yidong Bai', 18)}}的其他基金

The mitochondrial aspects of health disparity of hepatocellular carcinoma in Hispanic population
西班牙裔人群肝细胞癌健康差异的线粒体方面
  • 批准号:
    10729283
  • 财政年份:
    2023
  • 资助金额:
    $ 23.25万
  • 项目类别:
Characterization the disruption of mitochondrial function and induction of oxidative stress by SARS-CoV2
SARS-CoV2 对线粒体功能的破坏和氧化应激诱导的表征
  • 批准号:
    10510963
  • 财政年份:
    2022
  • 资助金额:
    $ 23.25万
  • 项目类别:
Characterization the disruption of mitochondrial function and induction of oxidative stress by SARS-CoV2
SARS-CoV2 对线粒体功能的破坏和氧化应激诱导的表征
  • 批准号:
    10874033
  • 财政年份:
    2022
  • 资助金额:
    $ 23.25万
  • 项目类别:
The role of Grp75 in supercomplex assembly and neurodegeneration
Grp75 在超复合物组装和神经退行性变中的作用
  • 批准号:
    9762142
  • 财政年份:
    2018
  • 资助金额:
    $ 23.25万
  • 项目类别:
Regulation of mitochondrial respiratory complex I dynamics
线粒体呼吸复合物 I 动力学的调节
  • 批准号:
    8762078
  • 财政年份:
    2014
  • 资助金额:
    $ 23.25万
  • 项目类别:
Regulation of mitochondrial respiratory complex I dynamics
线粒体呼吸复合物 I 动力学的调节
  • 批准号:
    8898851
  • 财政年份:
    2014
  • 资助金额:
    $ 23.25万
  • 项目类别:
Regulation of mitochondrial respiratory complex I
线粒体呼吸复合物 I 的调节
  • 批准号:
    8129567
  • 财政年份:
    2010
  • 资助金额:
    $ 23.25万
  • 项目类别:
Regulation of mitochondrial respiratory complex I
线粒体呼吸复合物 I 的调节
  • 批准号:
    8031712
  • 财政年份:
    2010
  • 资助金额:
    $ 23.25万
  • 项目类别:
Role of Mitochondrial DNA Mutations in Aging in Neuronal Cells
线粒体 DNA 突变在神经细胞衰老中的作用
  • 批准号:
    7191724
  • 财政年份:
    2006
  • 资助金额:
    $ 23.25万
  • 项目类别:
Role of Mitochondrial DNA Mutations in Aging in Neuronal Cells
线粒体 DNA 突变在神经细胞衰老中的作用
  • 批准号:
    7371075
  • 财政年份:
    2006
  • 资助金额:
    $ 23.25万
  • 项目类别:

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PTEN抑制A549肺癌细胞趋电性及调控直流电场对肺癌转移诱导的研究
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Toxicity evaluation and mechanism of acid gas generation from halogen fire extinguisher by combination of FTIR analysis and human cell A549 viability
结合 FTIR 分析和人体细胞 A549 活力评价卤素灭火器产生酸性气体的毒性和机制
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    26350465
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    2014
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An in vitro system has identified a factor released only by Pseudomonas aeruginosa biofilm and not planktonic bacteria that interacts with A549 lung epithelia and LL-37 pre-treatment of biofilms minimizes its effects.
体外系统已鉴定出仅由铜绿假单胞菌生物膜而不是浮游细菌释放的与 A549 肺上皮细胞相互作用的因子,并且生物膜的 LL-37 预处理可最大限度地减少其影响。
  • 批准号:
    263429
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    2012
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Mechanism for the release of IL-8 from A549 cells treated with alpha-toxin.
用 α 毒素处理的 A549 细胞释放 IL-8 的机制。
  • 批准号:
    21790431
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二恶英对芳烃受体(AhR)、Arnt和E2F基因转录调控A549细胞增殖过程及其机制
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