(GM2 gangliosidosis), in which a faulty β-hexosaminidase A leads to
the accumulation of the glycosphingolipid GM2 ganglioside in neu-
rones, causing death during childhood. In Danon disease, a vacuolar
skeletal myopathy and cardiomyopathy with neurodegeneration in
hemizygous males, lysosomes fail to fuse with autophagosomes because
of a mutation of the lysosomal membrane protein LAMP-2 (lysosomal B
associated membrane protein-2).
26S proteasome
Outer membrane
A protein can be degraded by different mechanisms, depending on
the cell type and different pathological conditions. Furthermore, the
same substrate can engage different proteolytic pathways (Park and Inner membrane
Cuervo 2013). Three major protein degradation mechanisms operate
in eukaryotic cells to dispose of non-functional cellular proteins: Cristae (folds)
the autophagosome–lysosomal pathway (see above); the apoptotic
procaspase–caspase pathway (see below); and the ubiquitinated Elementary
particles
protein–26S proteasome pathway. The 26S proteasome is a multicata-