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Chaperone-Mediated Autophagy Pathway (CMA)
- Target
- CMA
- Molecular classification
- Pathway
01
Overview
Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway responsible for the turnover of specific soluble cytosolic proteins. It targets individual proteins for direct translocation across the lysosomal membrane without vesicle intermediates. This process is crucial for maintaining cellular homeostasis, especially under stress conditions. Key components include substrate proteins with KFERQ-like motifs, the chaperone Hsc70, and the lysosomal receptor LAMP2A. Impairment or dysregulation of CMA has been linked to various diseases.
- Other names
- CMA pathway
02
Mechanism of action
Modulation of key components like Hsc70 or LAMP2A, NRF2 activators, p38–TFEB inhibitors
03
Biological functions
Protein quality controlRegulation of metabolismCellular response to stressAging processesImmune functionLysosomal degradation
04
Disease associations
Neurodegenerative diseases (e.g., Parkinson’s disease)CancerMetabolic disordersAge-related decline in cellular function
05
Safety considerations
Off-target effects on other autophagy pathwaysPotential for disrupting cellular homeostasisContext-dependent effects (activation vs. inhibition in different diseases)
06
Biomarkers
LAMP2A levelsKFERQ-containing substrate protein levelsHsc70 activity
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