Different mechanisms target intracellular components for their degradation into lysosomes through what is known as autophagy. In mammals, three main forms of autophagy have been described: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). CMA is the only autophagic pathway that allows selective degradation of soluble proteins in lysosomes. In contrast to the other mammalian forms of autophagy, CMA does not require vesicle formation or major changes in the lysosomal membrane. Instead, substrate proteins directly cross the lysosomal membrane to reach the lumen, where they are rapidly degraded. The substrate proteins are targeted to the lysosomal membrane by recognition of a targeting motif (a KFERQ-like motif), by a chaperone complex, consisting of hsc70 and its cochaperones, in the cytoplasm. Once at the lysosomal membrane, the protein interacts with a lysosomal receptor for this pathway, lysosomal associated membrane protein type 2A (LAMP-2A), and it is translocated across the membrane into the lysosomal lumen assisted by a lysosome resident chaperone. These two characteristics--selectivity and direct substrate translocation--determine the particular role of CMA in different physiological and pathological conditions. In this chapter, we cover current findings on the molecular mechanisms for CMA and the possible pathophysiological relevance of this selective lysosomal degradation.
Juvenile neuronal ceroid lipofuscinosis is caused by mutation of a novel, endosomal/lysosomal membrane protein encoded by CLN3. The observation that the mitochondrial ATPase sub...
Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are ...
Macroautophagy/autophagy is a conserved transport pathway where targeted structures are sequestered by phagophores, which mature into autophagosomes, and then delivered into lys...
The lysosomal degradation pathway of autophagy plays a fundamental role in cellular, tissue, and organismal homeostasis and is mediated by evolutionarily conserved autophagy-rel...
Autophagy is a process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for degradation and recy...
Social media, news, blog, policy document mentions