Autophagy-lysosomal system

Matsuda N, Tanaka K (2010) Does impairment of the ubiquitin-proteasome system or the autophagy-lysosome pathway predispose individuals to neurodegenerative disorders such as Parkinson s disease J Alzheimers Dis 19 1-9... 

Long-lived proteins. Evidence suggests that most of the cytosolic and membrane-bound proteins fall in this group. They have a compact structure and are fairly resistant to proteolytic attack. At the same time they appear to be continuously, if slowly, sequestered by the lysosomes, i.e. by autophagy. Thus the lysosomal system is believed to function as a general pathway for the breakdown of most enzymes and structural proteins to free amino acids. 

In addition to activated macroautophagy, our studies provided important evidence that autophagy related to lysosomal function is impaired in s-IBM muscle fibers. They showed a decrease of lysosomal cathepsin D and B enzymatic activities that appeared spedfic to s-IBM, because in polymyositis muscle fibers their activities were actually increased in our study [13] and in studies by others (referenced in [13]). In polymyositis macroautophagy was also increased but autophagic vacuoles and indusions do not form, perhaps because the lysosomal system may be functioning adequately. Our results also suggest that lymphocytic inflammation, which is... 

As an explanation for these findings, we have recently hypothesized that lysosomal autophagy accounts for the part of protein degradation that is sensitive to nutritional step-up and step-down (Knowles and Ballard, 1976). We envisage autophagy as a nonselective process in which all cytoplasmic constituents are degraded at a relatively slow rate. Variations in enzyme half-lives are explained by a second degra-dative system as yet uncharacterized, but possibly associated with... 

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