Chaperone‐mediated autophagy: Molecular mechanisms, biological functions, and diseases

Abstract

Chaperone‐mediated autophagy (CMA) is a lysosomal degradation pathway that eliminates substrate proteins through heat‐shock cognate protein 70 recognition and lysosome‐associated membrane protein type 2A‐assisted translocation. It is distinct from macroautophagy and microautophagy. In recent years, the regulatory mechanisms of CMA have been gradually enriched, including the newly discovered NRF2 and p38–TFEB signaling, as positive and negative regulatory pathways of CMA, respectively. Normal CMA activity is involved in the regulation of metabolism, aging, immunity, cell cycle, and other physiological processes, while CMA dysfunction may be involved in the occurrence of neurodegenerative disorders, tumors, intestinal disorders, atherosclerosis, and so on, which provides potential targets for the treatment and prediction of related diseases. This article describes the general process of CMA and its role in physiological activities and summarizes the connection between CMA and macroautophagy. In addition, human diseases that concern the dysfunction or protective role of CMA are discussed. Our review deepens the understanding of the mechanisms and physiological functions of CMA and provides a summary of past CMA research and a vision of future directions.

Potential application of traditional Chinese medicine in age-related macular degeneration—focusing on mitophagy

“…By assisting in the regulation of protein, nucleic acid, and lipid balances, the modulation of reactive oxidative stress and oxygen species (ROS), and the improvement of mitochondrial function, autophagy contributes to cellular metabolic needs and the renewal of intracellular organelles (Nita and Grzybowski, 2023). Depending on the intracellular lysosomal degradation mechanism, three distinct forms of autophagy-macroautophagy, microautophagy, and chaperone-mediated autophagy-have been distinguished (Mizushima, 2018;Yao and Shen, 2020) (Figure 1). Macroautophagy is the most predominant and conserved type of autophagy and proceeds via five stages-induction, nucleation, extension, fusion, and degradation (Nieto-Torres and Hansen, 2021).…”