Silvia Vega-Rubín-de-Celis, in Autophagy in Health and Disease (Second Edition), 2022 Chaperone-mediated autophagyĬMA is a form of autophagy in which substrates are directly targeted to the lysosome for degradation upon binding with the cytosolic chaperone HSC70 and further interaction with the cytosolic tail of the lysosome-associated membrane protein type 2. In this chapter, we will summarize the contemporary understanding of the basic characteristics, the molecular dynamics, the regulatory mechanisms and functions of CMA, and discuss the evidence the potential role for CMA defect in the pathogenesis of kidney diseases. Given the selective nature of proteolysis and its role in targeting the long-lived proteins, CMA is capable of influencing the levels of certain proteins under both physiological and pathological conditions. In addition, CMA is particularly relevant to the renal proximal tubules as CMA is by far the most predominant form of autophagy in the basal state of the mature tubule. Not surprisingly, disturbed CMA has been found in a number of diseases such as neurodegeneration, aging, oncogenesis, and diabetes mellitus. Of note, a vast number of cytosolic proteins can be degraded using the CMA mechanism, consolidating a central role for CMA under various pathophysiological conditions.

The hallmarks for CMA include absence of vesicle formation or membrane invagination in the process of protein delivery to lysosomes, since the target proteins may be directly translocated across the lysosomal membrane for degradation. Jun Ren, in Autophagy and Cardiometabolic Diseases, 2018 AbstractĬhaperone-mediated autophagy (CMA) denotes one of the intracellular proteolytic machineries for the selective degradation of cytosolic proteins within lysosomes.

Chaperone mediated autophagy