Impaired Turnover of Autophagolysosomes in Cathepsin L Deficiency

The study investigated the effects of cathepsin L (Ctsl) deficiency in mice, which led to the formation of large dysmorphic vesicles in various tissues, including the heart, thyroid, and skin, resulting in conditions like dilative cardiomyopathy and periodic hair loss. Researchers used primary mouse embryonic fibroblasts (MEF) from Ctsl-/- mice to explore the role of macroautophagy in these phenotypes. They found that while the initiation of autophagy and autophagosome-lysosome fusion were not significantly impaired, the degradation of autophagolysosomal content was hindered, leading to the accumulation of large, aberrant autophagolysosomes. This impairment was linked to elevated levels of cathepsin D and contributed to the pathological phenotypes observed in Ctsl-/- mice.