In fact, studies in experimental animal models, or in certain pathologies, have revealed that failure of the autophagic system results in marked accumulation of abnormal proteins and defective organelles, which leads to functional failure, and often to cell death ( 1, 3). Under basal cellular conditions, the fine-tuned balance between protein synthesis and degradation contributes to the maintenance of cellular homeostasis and guarantees continuous renewal of proteome and organelles ( 2). Better molecular characterization of the different components of this pathway in recent years, along with the development of transgenic models with modified CMA activity and the identification of CMA dysfunction in different severe human pathologies and in aging, are all behind the recent regained interest in this catabolic pathway.Īutophagy (from Greek, “self-eating”) is a highly regulated cellular process that mediates the degradation of intracellular components-single macromolecules and organelles-inside lysosomes ( 1). Substrate proteins undergo unfolding and translocation across the lysosomal membrane before reaching the lumen, where they are rapidly degraded. Selectivity in CMA is conferred by the presence of a targeting motif in the cytosolic substrates that, upon recognition by a cytosolic chaperone, determines delivery to the lysosomal surface. In this review, we focus on chaperone-mediated autophagy (CMA), a selective form of autophagy that modulates the turnover of a specific pool of soluble cytosolic proteins. Different pathways contribute to the degradation of intracellular components in lysosomes or autophagy. In fact, failure to timely turnover proteins and organelles leads often to cell death and disease. Continuous renewal of intracellular components is required to preserve cellular functionality.
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