Highlights d BALF cell transcriptome indicates robust innate immune responses in COVID-19 patients d COVID-19 patients exhibit chemokine-dominant hypercytokinemia d ISGs are highly expressed in COVID-19 patients and exhibit pathogenic potential

SUMMARY The mitochondrion is the primary source of reactive oxygen species (ROS) in eukaryotic cells. With the aid of a novel mitochondrial matrix-targeted superoxide indicator, here we show that individual mitochondria undergo spontaneous bursts of superoxide generation, termed “superoxide flashes”. Superoxide flashes occur randomly in space and time, exhibit all-or-none properties, and reflect elementary events of superoxide production within single mitochondria across a wide diversity of cells. Individual flashes are triggered by transient openings of the mitochondrial permeability transition pore (mPTP) and are fueled by electron transfer complexes-dependent superoxide production. While decreased during cardiac hypoxia/anoxia, a flurry of superoxide flash activity contributes to the destructive rebound ROS burst observed during early reoxygenation after anoxia. The discovery of superoxide flashes reveals a novel mechanism for quantal ROS production by individual mitochondria and substantiates the central role of mPTP in oxidative stress related pathology in addition to its well-known role in apoptosis.

We have purified distinct complexes of nine to 12 proteins [referred to as BRG1‐associated factors (BAFs)] from several mammalian cell lines using an antibody to the SWI2‐SNF2 homolog BRG1. Microsequencing revealed that the 47 kDa BAF is identical to INI1. Previously INI1 has been shown to interact with and activate human immunodeficiency virus integrase and to be homologous to the yeast SNF5 gene. A group of BAF47‐associated proteins were affinity purified with antibodies against INI1/BAF47 and were found to be identical to those co‐purified with BRG1, strongly indicating that this group of proteins associates tightly and is likely to be the mammalian equivalent of the yeast SWI‐SNF complex. Complexes containing BRG1 can disrupt nucleosomes and facilitate the binding of GAL4‐VP16 to a nucleosomal template similar to the yeast SWI‐SNF complex. Purification of the complex from several cell lines demonstrates that it is heterogeneous with respect to subunit composition. The two SWI‐SNF2 homologs, BRG1 and hbrm, were found in separate complexes. Certain cell lines completely lack BRG1 and hbrm, indicating that they are not essential for cell viability and that the mammalian SWI‐SNF complex may be tailored to the needs of a differentiated cell type.