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Studies on the mechanisms of autophagy: maturation of the autophagic vacuole

By W. A. Dunn


Abstract. Data presented in the accompanying paper suggests nascent autophagic vacuoles are formed from RER (Dunn, W. A. 1990. J. Cell Biol. 110:1923-1933). In the present report, the maturation of newly formed or nascent autophagic vacuoles into degradative vacuoles was examined using morphological and biochemical methods combined with immunological probes. Within 15 min of formation, autophagic vacuoles acquired acid hydrolases and lysosomal membrane proteins, thus becoming degradative vacuoles. A previously undescribed type of autophagic vacuole was also identified having characteristics of both nascent and degradative vacuoles, but was different from lysosomes. This intermediate compartment contained only small amounts of cathepsin L in comparison to lysosomes and was bound by a double membrane, typical of nascent vacuoles. However, unlike nascent vacuoles yet comparable to degradative vacuoles, these vacuoles p ROT E! N S are degraded by nonlysosomal and lysosomal mechanisms (13, 26, 28, 29). The cytoplasmic pathway involves ubiquitin targeting of susceptible proteins followed by proteasome hydrolysis (13). The endoplasmic reticulum and sarcoplasmic reticulum have been implicated in the degradation of abnormal, poorly folded proteins that have not oligomerized into functional proteins (22, 33). Proteins are believed to enter lysosomes by one of the following routes: lysosome membrane invagination (microautophagy), prp73-mediated transport, and fusion of lysosomes with endocyti

Year: 1990
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