Secondary Mitochondrial Dysfunction in Gaucher Disease Type I, II and III-Review of the Experimental and Clinical Evidence.

ABSTRACT: Gaucher disease (GD) is an autosomal recessive metabolic disorder caused by pathogenic variants in the GBA1 gene, which encodes the lysosomal hydrolase β-glucocerebrosidase (GCase). The pathogenic defects result in a misfolded protein, which can trigger endoplasmic reticulum stress and an unfolded protein response within the affected cells. The reduced enzyme activity leads to accumulation of its substrates, glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph), within lysosomes or macrophages and with prominent disease manifestations in reticuloendothelial tissues such as liver, spleen and bone marrow. GCase defects alter both the mitochondria and the lysosome. In the lysosome, reduced GCase activity leads to glycosphingolipid build-up, disrupting lysosomal function and autoph

SUBMITTER: Dewsbury M 

PROVIDER: S-EPMC12652696 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature