Cells ensure the selective degradation of specific proteins while maintaining overall proteostasis through a process called protein quality control. This system involves various mechanisms that target damaged or misfolded proteins for degradation, while preserving the stability and functionality of essential proteins within the cell.
Protein Quality Control Mechanisms
- Chaperone-mediated protein folding: Chaperone proteins assist in the correct folding of newly synthesized proteins to prevent misfolding and aggregation.
- Ubiquitin-proteasome system: Ubiquitin molecules are attached to damaged or misfolded proteins, targeting them for degradation by the proteasome.
- Autophagy: Autophagy is a process where damaged organelles or protein aggregates are engulfed by autophagosomes and delivered to lysosomes for degradation.
Selective Protein Degradation
Cells use specific mechanisms to selectively target proteins for degradation while sparing others:
- Ubiquitin ligases: These enzymes recognize specific substrates and attach ubiquitin molecules to target proteins for degradation.
- Proteasome subunits: Different proteasome subunits recognize ubiquitinated proteins and degrade them in a controlled manner.
- Autophagy receptors: These proteins recognize specific cargo for degradation via autophagy, ensuring selective protein turnover.
Maintaining Proteostasis
Proteostasis is the balance between protein synthesis, folding, and degradation within the cell. To maintain proteostasis, cells employ the following strategies:
- Heat shock response: Cells upregulate chaperone proteins in response to stress, aiding in protein folding and preventing aggregation.
- Protein degradation pathways: The ubiquitin-proteasome system and autophagy help clear out damaged proteins to maintain overall protein turnover.
- Regulation of protein synthesis: Cells control the rate of protein synthesis to prevent the accumulation of misfolded or damaged proteins.
Cellular Responses to Proteotoxic Stress
When cells experience proteotoxic stress, such as an accumulation of misfolded proteins, they activate various stress response pathways to restore proteostasis:
- Unfolded protein response (UPR): UPR pathways are activated to increase protein folding capacity and reduce protein synthesis during stress conditions.
- Heat shock response: Heat shock proteins are upregulated to help refold damaged proteins or target them for degradation.
- Autophagy induction: Autophagy is upregulated to clear out protein aggregates and damaged organelles under stress conditions.