chaperone-mediated autophagy

Definition

Target type: biologicalprocess

The autophagy process which begins when chaperones and co-chaperones recognize a target motif and unfold the substrate protein. The proteins are then transported to the lysosome where they are degraded. [GOC:pad, GOC:PARL, PMID:22743996, PMID:23434281]

Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway that plays a crucial role in maintaining cellular homeostasis and responding to stress. Unlike other forms of autophagy, CMA does not involve the formation of autophagosomes. Instead, it relies on the direct interaction of specific protein substrates with a chaperone protein called heat shock cognate protein 70 (HSC70).

The process begins with the recognition of CMA substrates. These substrates typically contain a KFERQ-like motif, which is recognized by HSC70. Once bound, HSC70 delivers the substrate to the lysosomal membrane protein, LAMP-2A. LAMP-2A acts as a receptor for CMA substrates, facilitating their translocation across the lysosomal membrane.

The translocation process requires the concerted action of several other proteins, including lysosomal associated protein type 2 (LAPTM4A), which assists in the unfolding of the substrate, and the chaperone protein, Hsc70, which is associated with LAMP-2A and assists in substrate movement.

Once inside the lysosome, the substrate is degraded by lysosomal enzymes, which break it down into amino acids and other small molecules. These products can then be recycled back into the cell for use in other metabolic processes.

CMA plays a critical role in various cellular functions, including:

* **Protein quality control:** CMA removes damaged or misfolded proteins, preventing their accumulation and potential toxicity.
* **Cellular adaptation to stress:** CMA helps cells cope with environmental stress, such as nutrient deprivation or oxidative stress, by degrading unnecessary or damaged proteins.
* **Regulation of cellular signaling pathways:** CMA can regulate the activity of signaling proteins by degrading specific substrates.
* **Organelle turnover:** CMA participates in the degradation of damaged or unnecessary organelles, contributing to cellular renewal.

Dysregulation of CMA has been implicated in various diseases, including neurodegenerative disorders, cancer, and aging. Understanding the intricate mechanisms of CMA is crucial for developing therapeutic strategies targeting this pathway to treat these diseases.'
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Proteins (2)

Compounds (66)