Figure 1. (A) Lysosome-competent cells. Under normal conditions, LPS activates pexophagy and induces a biphasic expression response, with an early decrease followed by later upregulation of ABCD3 and PEX14, and increased proliferation of peroxisomes. Both, H₂O₂-generating ACOX and H₂O₂-decomposing CAT are decreased, thus preserving peroxisomal H₂O₂ equilibrium. (B) Lysosome-defective cells. Lysosomal dysfunction inhibits pexophagy, which results in a higher number of peroxisomes under basal conditions. LPS stimulation of lysosome-defective cells does not affect peroxisomal turnover. Cells with accumulated dysfunctional peroxisomes exhibit impaired enzymatic activity of CAT, which together with functioning ACOX creates H₂O₂ disequilibrium and enhances oxidative stress. Later, this metabolic-oxidative imbalance results in a global deterioration of peroxisomal functions— peroxisomal burnout—and in an aggravated organ injury.