Mitochondria and microbiota dysfunction in COVID-19 pathogenesis.
Mitochondria and microbiota dysfunction in COVID-19 pathogenesis.
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DOI：
10.1016/j.mito.2020.06.008
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发表时间：
2020-09
期刊：
影响因子：
4.4
通讯作者：
Edeas M
中科院分区：
文献类型：
--
作者：
Saleh J;Peyssonnaux C;Singh KK;Edeas M
由冠状病毒（SARS-CoV-2）引起的COVID-19大流行令世界措手不及，陷入发病率和死亡率压倒性的重大危机。这种高度传染性的疾病与呼吸衰竭有关，在其他冠状病毒感染中不常见。越来越多的证据表明，COVID-19患者的疾病加速进展与被称为“细胞因子风暴”的高度炎症状态有关，涉及重大全身性扰动。这些包括铁失调，表现为与疾病严重程度相关的高铁蛋白血症。铁失调诱导活性氧（ROS）的产生，促进氧化应激。线粒体是细胞氧化平衡的枢纽。此外，线粒体可以在无核血小板、细胞外囊泡中“无细胞”循环，并且线粒体DNA存在于细胞外空间中。升高的炎症/氧化状态可能导致线粒体功能障碍，从而导致血小板损伤和细胞凋亡。功能障碍的血小板与凝血级联反应的相互作用加剧了凝血事件和血栓形成。此外，线粒体氧化应激可能导致微生物群生态失调，改变凝血途径并刺激炎症/氧化反应，导致事件的恶性循环。在这里，我们讨论了由SARS-CoV-2引起的各种细胞和系统事件，这些事件可能严重影响细胞内和细胞外线粒体功能，并导致疾病的进展和严重程度。了解这些关键调节剂如何影响COVID-19发病机制，以确定可能减少疾病致命结局的新治疗靶点至关重要。
The COVID-19 pandemic caused by the coronavirus (SARS-CoV-2) has taken the world by surprise into a major crisis of overwhelming morbidity and mortality. This highly infectious disease is associated with respiratory failure unusual in other coronavirus infections. Mounting evidence link the accelerated progression of the disease in COVID-19 patients to the hyper-inflammatory state termed as the “cytokine storm” involving major systemic perturbations. These include iron dysregulation manifested as hyperferritinemia associated with disease severity. Iron dysregulation induces reactive oxygen species (ROS) production and promotes oxidative stress. The mitochondria are the hub of cellular oxidative homeostasis. In addition, the mitochondria may circulate “cell-free” in non-nucleated platelets, in extracellular vesicles and mitochondrial DNA is found in the extracellular space. The heightened inflammatory/oxidative state may lead to mitochondrial dysfunction leading to platelet damage and apoptosis. The interaction of dysfunctional platelets with coagulation cascades aggravates clotting events and thrombus formation. Furthermore, mitochondrial oxidative stress may contribute to microbiota dysbiosis, altering coagulation pathways and fueling the inflammatory/oxidative response leading to the vicious cycle of events. Here, we discuss various cellular and systemic incidents caused by SARS-CoV-2 that may critically impact intra and extracellular mitochondrial function, and contribute to the progression and severity of the disease. It is crucial to understand how these key modulators impact COVID-19 pathogenesis in the quest to identify novel therapeutic targets that may reduce fatal outcomes of the disease.
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影响因子：
1.5
作者：
Hayashi, T.;Tanaka, S.;Inoue, M.
通讯作者：
Inoue, M.
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1126/science.1201940
发表时间：
2011-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Kroemer G
影响因子：
8.4
作者：
Edeas, Marvin;Saleh, Jumana;Peyssonnaux, Carole
通讯作者：
Peyssonnaux, Carole
影响因子：
5.2
作者：
Herst PM;Rowe MR;Carson GM;Berridge MV
通讯作者：
Berridge MV