NCOA4-Mediated Ferritinophagy: A Vicious Culprit in COVID-19 Pathogenesis?

Fengju Jia,Hongxia Liu,Shan Kang

doi:10.3389/fmolb.2021.761793

Abstract

Coronavirus disease 2019 (COVID-19) is a global pandemic that has caused widespread loss of life. Notably, in this disease, severe inflammatory reactions characterized by cytokine storms are caused by severe acute respiratory syndrome coronavirus 2. The cytokine storms may promote hyper-ferritinemia which can further intensify the inflammation. Moreover, elevated ferritin levels trigger nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, in which ferritin is degraded and iron is released. Excess iron released from ferritinophagy can promote ferroptosis and cellular damage. Therefore, we propose that NCOA4-mediated ferritinophagy can be targeted to limit the ferroptosis and prevent the multi-organ damage and severity in COVID-19 patients.

Highlights

Coronavirus disease 2019 (COVID-19), triggered by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious health concern and can be profoundly detrimental
The SARS-CoV-2 RNA is recognized by the pathogen recognition receptors, which trigger a downstream cascade of molecules leading to the activation of transcription factors, such as nuclear factor kappa B and interferon regulatory factor 3 (IRF-3) and the subsequent production of type 1 interferons and several other pro-inflammatory cytokines (Kawai and Akira, 2010; Conti et al, 2020; Yang et al, 2020)
Elevated plasma levels of plasma pro-inflammatory cytokines, such as IL-6, IL2, IL-7, IL-10, IFN-γ–induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 alpha (MIP-1α), have been observed in some patients (Han et al, 2020; Karki et al, 2021). This expansion of an uncontrolled inflammatory response due to SARS-CoV-2 infection potentially leads to cell death by apoptosis, necrosis, or ferroptosis, resulting in multi-organ damage in patients with COVID-19 (Banchini et al, 2021)

Summary

Introduction

Coronavirus disease 2019 (COVID-19), triggered by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious health concern and can be profoundly detrimental. A significant proportion of patients with COVID-19 experience severe interstitial pneumonia, possibly resulting in acute respiratory distress syndrome and systemic inflammatory response syndrome. COVID-19 systemic inflammatory reaction can be life-threatening due to its hyper-inflammation sustained by a cytokine storm.

Results

Conclusion