Comparison of mitochondrial response to SARS-CoV-2 spike protein receptor binding domain in human lung microvascular, coronary artery endothelial and bronchial epithelial cells
Recent evidence indicate that SARS-CoV-2 spike protein affects mitochondria with a cell type-dependent outcome. We elucidate the effect of SARS-CoV-2 receptor binding domain (RBD) on the mitochondrial network and cristae morphology, oxygen consumption, mitoROS production, and inflammatory cytokine expression in cultured human lung microvascular (HLMVEC) and coronary artery endothelial (HCAEC) and bronchial epithelial cells (HBEC). Live Mito Orange staining, STED microscopy and Fiji MiNa analysis were used for mitochondrial cristae and network morphometry, Agilent XFp analyser for mitochondrial/glycolytic activity, MitoSOX fluorescence for mitochondrial ROS, and qRT-PCR plus Luminex for cytokines. In HLMVEC, SARS-CoV-2 RBD fragmented the mitochondrial network, decreased cristae density, mitochondrial oxygen consumption and glycolysis and induced mitoROS-mediated GM-CSF and IL-1{beta} expression in all three investigated cell types and IL-8 - in both endothelial cell types. Mitochondrial ROS control SARS-CoV-2 RBD-induced inflammation in HLMVEC, HCAEC and HBEC, with the mitochondria of HLMVEC being more sensitive to SARS-CoV-2 RBD.