dc.description.abstracteng | This work examined (a) how the endotoxic stress affects peroxisomal function and autophagic degradation of peroxisomes-pexophagy, (b) how a superimposed dysfunction of lysosomes and pexophagy modifies responses to lipopolysaccharide, and (c) the mechanisms of peroxisomal contribution to renal injury. To accomplish this, we used lysosome-defective mice in vivo and primary endothelial cells in vitro, and compared the responses with wild-type littermates.
We demonstrated that pexophagy is a default response to endotoxic injury. However, when lysosomal dysfunction (a frequent companion of chronic diseases) is superimposed, recycling and functioning of peroxisomes are impaired, and an imbalance between hydrogen peroxide-generating β-oxidation and hydrogen peroxide-detoxifying catalase ensues, which ultimately results in peroxisomal burnout.
Our data strongly suggest that pexophagy, a cellular mechanism per se, is essential in functional maintenance of peroxisomes during lipopolysaccharide exposure. Inhibition of pexophagy results in accumulation of impaired peroxisomes, redox disequilibrium, and aggravated renal damage. | de |