Amity Institute of Biotechnology, Amity University, Plot No: 36, 37 & 38, Major Arterial Road, Action Area II, Kadampukur Village, Newtown, Kolkata, 700135, West Bengal, India.
Indian Association for the Cultivation of Science, Jadavpur, 700032, Kolkata, India.
Mol Cell Biochem. 2023 Jun;478(6):1325-1343. doi: 10.1007/s11010-022-04593-z. Epub 2022 Oct 29.
SARS-CoV-2 is a positive-strand RNA virus that infects humans through the nasopharyngeal and oral route causing COVID-19. Scientists left no stone unturned to explore a targetable key player in COVID-19 pathogenesis against which therapeutic interventions can be initiated. This article has attempted to review, coordinate and accumulate the most recent observations in support of the hypothesis predicting the altered state of mitochondria concerning mitochondrial redox homeostasis, inflammatory regulations, morphology, bioenergetics and antiviral signalling in SARS-CoV-2 infection. Mitochondria is extremely susceptible to physiological as well as pathological stimuli, including viral infections. Recent studies suggest that SARS-CoV-2 pathogeneses alter mitochondrial integrity, in turn mitochondria modulate cellular response against the infection. SARS-CoV-2 M protein inhibited mitochondrial antiviral signalling (MAVS) protein aggregation in turn hinders innate antiviral response. Viral open reading frames (ORFs) also play an instrumental role in altering mitochondrial regulation of immune response. Notably, ORF-9b and ORF-6 impair MAVS activation. In aged persons, the NLRP3 inflammasome is over-activated due to impaired mitochondrial function, increased mitochondrial reactive oxygen species (mtROS), and/or circulating free mitochondrial DNA, resulting in a hyper-response of classically activated macrophages. This article also tries to understand how mitochondrial fission-fusion dynamics is affected by the virus. This review comprehends the overall mitochondrial attribute in pathogenesis as well as prognosis in patients infected with COVID-19 taking into account pertinent in vitro, pre-clinical and clinical data encompassing subjects with a broad range of severity and morbidity. This endeavour may help in exploring novel non-canonical therapeutic strategies to COVID-19 disease and associated complications.
SARS-CoV-2 是一种正链 RNA 病毒，通过鼻咽和口腔途径感染人类，导致 COVID-19。科学家们不遗余力地探索 COVID-19 发病机制中的可靶向关键参与者，以便可以针对该靶点启动治疗干预。本文试图综述、协调和积累最新观察结果，以支持有关 SARS-CoV-2 感染中线粒体氧化还原稳态、炎症调节、形态、生物能量和抗病毒信号改变的假说。线粒体极易受到生理和病理刺激的影响，包括病毒感染。最近的研究表明，SARS-CoV-2 发病机制会改变线粒体的完整性，进而线粒体调节细胞对感染的反应。SARS-CoV-2 的 M 蛋白抑制线粒体抗病毒信号 (MAVS) 蛋白聚集，从而阻碍先天抗病毒反应。病毒开放阅读框 (ORF) 也在改变线粒体对免疫反应的调节中发挥重要作用。值得注意的是，ORF-9b 和 ORF-6 会损害 MAVS 的激活。在老年人中，由于线粒体功能受损、线粒体活性氧 (mtROS) 增加和/或循环游离线粒体 DNA，NLRP3 炎性体过度激活，导致经典激活的巨噬细胞过度反应。本文还试图了解病毒如何影响线粒体裂变-融合动力学。本文综述了 COVID-19 感染者发病机制和预后中的整体线粒体特征，同时考虑了涵盖广泛严重程度和发病率的体外、临床前和临床相关数据。这一努力可能有助于探索针对 COVID-19 疾病及其相关并发症的新型非经典治疗策略。
