The properties of the mitochondrial F1FO‐ATPase catalytic site, which can bind Mg2+, Mn2+, or Ca2+ and hydrolyze ATP, were explored by inhibition kinetic analyses to cast light on the Ca2+‐activated F1FO‐ATPase connection with the permeability transition pore (PTP) that initiates cascade events leading to cell death. While the natural cofactor Mg2+ activates the F1FO‐ATPase in competition with Mn2+, Ca2+ is a noncompetitive inhibitor in the presence of Mg2+. Selective F1 inhibitors (Is‐F1), namely NBD‐Cl, piceatannol, resveratrol, and quercetin, exerted different mechanisms (mixed and uncompetitive inhibition) on either Ca2+‐ or Mg2+‐activated F1FO‐ATPase, consistent with the conclusion that the catalytic mechanism changes when Mg2+ is replaced by Ca2+. In a partially purified F1 domain preparation, Ca2+‐activated F1‐ATPase maintained Is‐F1 sensitivity, and enzyme inhibition was accompanied by the maintenance of the mitochondrial calcium retention capacity and membrane potential. The data strengthen the structural relationship between Ca2+‐activated F1FO‐ATPase and the PTP, and, in turn, on consequences, such as physiopathological cellular changes.
Sero-epidemiological surveys are valuable attempts to estimate the circulation of SARS-CoV-2 in general or selected populations. Within this context, a prospective observational study was conducted to estimate the prevalence and persistence of SARS-CoV-2 antibodies in different categories of workers and factors associated with positivity, through the detection of virus-specific immunoglobulin G and M (IgG/IgM) in serum samples. Enrollees were divided in low exposure and medium-high groups on the basis of their work activity. Antibody responders were re-contacted after 3 months for the follow-up. Of 2255 sampled workers, 4.8% tested positive for SARS-CoV-2 IgG/IgM antibodies, with 81.7% to IgG only. Workers who continued to go to their place of work, were healthcare workers, or experienced at least one COVID-19-related symptom were more likely to test positive for SARS-CoV-2 antibodies. SARS-CoV-2 antibodies prevalence was significantly higher in the medium-high risk vs. low-risk group (7.2% vs. 3.0%, p < 0.0001). At 3-month follow-up, 81.3% of subjects still had antibody response. This study provided important information of SARS-CoV-2 infection prevalence among workers in northern Italy, where the impact of COVID-19 was particularly intense. The presented surveillance data give a contribution to refine current estimates of the disease burden expected from the SARS-CoV-2.
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