Mitochondria as a Critical Target of COVID-19 Pathogenesis

Abstract

Over the past two years, findings from several research studies published in highly influential journals pointed to a critical involvement of mitochondria in the pathophysiology of SARS-CoV2 infections. Among the most exciting findings are the involvement of (i) the “mitochondrial ROS–HIF-1α –glycolysis” axis, (ii) the “cGAS–STING” signaling, and (iii) the “mitochondrial apoptotic cell death” pathway.

(First online: March 3, 2022)

REFERENCES                      

1. Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004; 116(2):205–19. doi: https://dx.doi.org/10.1016/s0092-8674(04)00046-7
2. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 2014; 94(3):909–50. doi: https://dx.doi.org/10.1152/physrev.00026.2013
3. Ros EO. Mitochondrial ROS take center stage in immune regulation. React Oxyg Species (Apex) 2021; 11:n9–n10. doi: https://dx.doi.org/10.20455/ros.2021.n.809
4. Weinberg SE, Sena LA, Chandel NS. Mitochondria in the regulation of innate and adaptive immunity. Immunity 2015; 42(3):406–17. doi: https://dx.doi.org/10.1016/j.immuni.2015.02.002
5. Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1alpha/glycolysis-dependent axis. Cell Metab 2020; 32(3):437–46 e5. doi: https://dx.doi.org/10.1016/j.cmet.2020.07.007
6. Domizio JD, Gulen MF, Saidoune F, Thacker VV, Yatim A, Sharma K, et al. The cGAS-STING pathway drives type I IFN immunopathology in COVID-19. Nature 2022. doi: https://dx.doi.org/10.1038/s41586-022-04421-w
7. Simpson DS, Pang J, Weir A, Kong IY, Fritsch M, Rashidi M, et al. Interferon-gamma primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway. Immunity 2022. doi: https://dx.doi.org/10.1016/j.immuni.2022.01.003