Fig 1: The impact of COVID-19 infection on oxygen homeostasis. Under normal aerobic conditions, HIF-1 regulates glucose metabolism resulting in pyruvate formation. Pyruvate dehydrogenase (PDH) converts pyruvate to acetyl-CoA for the entry into the TCA cycle. Under hypoxic and/or COVID-19 infection conditions, HIF-1 targets and activates many glycolytic enzymes including lactate dehydrogenase (LDH) to increase lactate production. HIF-1 also promotes pyruvate dehydrogenase kinase (PDK) to inactivate PDH which prohibits the conversion of pyruvate to acetyl-CoA. Under these infection conditions, the ETC becomes a source for reactive oxygen species (ROS) which stabilize HIF-1. Impairment of the ETC leads to significant depletion in the levels of ATP synthase subunit alpha (Atp5a1) responsible for producing ATP through mitochondrial complex V, and the ADP/ATP translocase (Slc25a4). Both proteins are regulated via HIF-1α.
Fig 2: Atp5a1 (ATP synthase subunit alpha) and Slc25a4 (ADP/ATP translocase) are decreased in SARS-CoV-2-infected hamsters. (A,C) Representative MS2 spectra of infected versus control hamsters for a peptide assigned to Atp5a1 (panel (A), tryptic peptide sequence ISEQSDAK corresponding to residues 532–539 in UniProt accession number F1T2M2) and Slc25a4 (panel C, tryptic peptide sequence LAADVGK from residues 141–147 in UniProt accession number A0A1U7QFU8) in infected (left) versus control (right) hamsters. (B,D) Bar graphs show mean values for the mass spectrometry-based quantification of Atp5a1 from 21 peptides (panel (B) and Slc25a4 from 3 peptides panel (D)). Statistical analysis was by a Student’s t test as described in the Methods. Error bars indicate SD.
Supplier Page from Abcam for ATP synthase Activity Assay Kit (Colorimetric)