ApoA-IIowa fibrils were degraded via the autophagy-lysosomal pathway in human embryonic kidney (HEK) 293 cells, which resulted in a loss of lysosomal acidity and in the cytosolic release of the lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils was reversed by enhancing the degradation of apoA-IIowa fibrils and inhibiting cathepsin B. Our results thus emphasize the importance of autophagy and lysosomes in the pathology of AApoA1 amyloidosis. This evidence concerns the gene CTSB and amyloidosis.