Also, the ESCRT complex present in the membrane of late endosomes can form multivesicular bodies (MVBs) containing the cargo to be degraded. Microautophagy, that in mammals involves the invagination of proteins (blue) that may contain a KFERQ-like motif recognized by Hsc70. Later, the Autophagosome fuses with the lysosome membrane forming the Autolysosome where the cargo will be degraded by cathepsins and other lysosomal proteases 2. Macroautophagy can degrade individual proteins and complete organelles by engulfing them within an initial membrane called Phagophore, this membrane closes forming the Autophagosome vesicle. įigure 1 Scheme of three main autophagic pathways. However, Microautophagy, does not requires Lamp2A as protein receptor ( Figure 1). In the case of Microautophagy and CMA, both pathways need the interaction between the KFERQ-like motive in the protein substrate and the Hsc70 for target degradation. There are three main routes where different cargos arrive to the lysosomes ( Figure 1): i) Macroautophagy (MA) the cargo is trapped in double membrane vesicles known as phagosomes or autophagosomes that then fuse with the lysosome for the final cargo degradation ( 2) ii) Microautophagy, the lysosomes directly engulf cargo by membrane invagination (yeast) or late endosomes that form multivesicular bodies (mammals) to capture specific cytosolic components and then fuse with the lysosome for its degradation ( 3, 4) and (iii) Chaperone-mediated autophagy (CMA), there are no trafficking membranous vesicles involved, instead, cargo is selectively recognized by a chaperone protein and then internalized into the lysosome for its degradation ( 5). Further, it will help to define whether the attention of the investigation should be focused on Lamp2A and Hsc70 because they can have an independent role in cancer progression beyond of their participation in altered CMA activity.Īutophagy is a lysosomal dependent cellular pathway that mediates the degradation of organelles, protein aggregates and specific proteins, and is essential for cell survival, development and homeostasis ( 1). This analysis will help to better understand the role of CMA activity in cancer and to elucidate whether CMA can be considered as target for therapeutics. In particular, this review will discuss about the evidences in which alterations CMA components Lamp2A and Hsc70 are associated or not with changes in CMA activity in different cancer types. The objective of this review is to discuss whether altering the CMA activity, CMA substrates or CMA components is accurate to avoid cancer progression. However, changes in the expression levels of these CMA components are not always associated with changes in CMA activity and their biological significance must be carefully interpreted case by case. In cancer, alterations of the CMA principal components, Hsc70 and Lamp2A protein and mRNA levels, have been described in malignant cells. The role of CMA in different physiopathological processes has been studied for several years. 4Autophagy Research Center (ARC), Santiago, ChileĬhaperone-mediated autophagy (CMA) represents a specific way of lysosomal protein degradation and contrary to macro and microautophagy is independent of vesicles formation.3San Sebastian University, Santiago, Chile.2Fundación Ciencia & Vida, Santiago, Chile.1Molecular and Cellular Pathology Laboratory, Dentistry Faculty, Institute in Dentistry Sciences, University of Chile, Santiago, Chile.Javiera Rios 1† Alvaro Sequeida 1† Amelina Albornoz 2,3 Mauricio Budini 1,4*
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