aggrephagy

Definition

Target type: biologicalprocess

The selective degradation of protein aggregates by macroautophagy. [GOC:autophagy, GOC:kmv, PMID:18508269, PMID:25062811]

Aggrephagy is a specialized form of macroautophagy, a cellular process responsible for the degradation and recycling of cellular components. Specifically, aggrephagy targets protein aggregates, which are clumps of misfolded or aggregated proteins that can accumulate in cells due to various stressors like aging, oxidative stress, or mutations. These aggregates are often toxic to cells and can contribute to the development of diseases such as Alzheimer's and Parkinson's.

Aggrephagy begins with the formation of a double-membrane vesicle called an autophagosome. This vesicle engulfs the protein aggregates, isolating them from the rest of the cell. The autophagosome then fuses with another cellular organelle called a lysosome. Lysosomes contain a variety of hydrolytic enzymes that break down the aggregated proteins into their constituent amino acids. These amino acids can then be reused by the cell to build new proteins.

Several key proteins play crucial roles in the aggrephagy process. For instance, chaperone proteins, such as Hsp70 and Hsp40, assist in recognizing and binding to misfolded proteins, tagging them for degradation. Other proteins, such as p62, act as adaptor proteins that link the aggregates to the autophagosome membrane.

The regulation of aggrephagy is complex and involves numerous signaling pathways. One important regulator is the mTOR pathway, which is activated by nutrients and growth factors. When activated, mTOR suppresses autophagy, including aggrephagy. However, when cells are under stress, such as starvation or oxidative stress, mTOR is inhibited, leading to the activation of aggrephagy.

Aggrephagy is essential for maintaining cellular homeostasis and preventing the accumulation of toxic protein aggregates. Deficiencies in aggrephagy are linked to the development of several neurodegenerative diseases, underscoring its critical role in cellular health.'
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Proteins (2)

Compounds (10)