AAT Bioquest

What are the main degradation pathways in eukaryotes?

Posted September 20, 2023


There are two main degradation pathways in eukaryotes - the ubiquitin-proteasome pathway and lysosomal proteolysis.

Ubiquitin-Proteasome Pathway

The Ubiquitin-Proteasome Pathway is the principal pathway for the targeted and rapid degradation of specific proteins within eukaryotic cells. 

This degradation pathway uses ubiquitin, a 76-amino-acid polypeptide that is highly conserved in all eukaryotes. Ubiquitin serves as a marker to designate specific cytosolic and nuclear proteins for degradation.

Ubiquitin attaches to a lysine residue's amino group on the protein to mark proteins to be broken down. Subsequent attachments of additional ubiquitin molecules results in the formation of a polyubiquitin chain. Proteasome, a large multi-subunit protease complex, recognizes and breaks down proteins with polyubiquitin chains, releasing ubiquitin in the process. The released ubiquitin can be reused in other cycles. 

A distinct characteristic of this degradation pathway is that both phases – the attachment of ubiquitin and the degradation of marked proteins – require energy, which is provided in the form of adenosine triphosphate (ATP).

Lysosomal Proteolysis

The lysosomal proteolysis pathway is a more generalized and gradual protein degradation process. 

A distinctive feature of lysosomal proteolysis is the uptake of proteins by membrane-enclosed organelles called lysosomes. Lysosomes, which contain various digestive enzymes including several proteases, play multiple roles in cell metabolism, including the digestion of extracellular proteins acquired through endocytosis and the gradual turnover of cytosolic proteins and cytoplasmic organelles.

For cellular proteins to undergo degradation through lysosomal proteolysis, they are first engulfed by lysosomes, often via autophagy. This involves the creation of autophagosomes or vesicles that enclose small portions of cytoplasm and cytoplasmic organelles within membranes derived from the endoplasmic reticulum. 

These autophagosomes subsequently fuse with lysosomes and their contents come in contact with and are digested by degradative lysosomal enzymes. The nonselective uptake of proteins into autophagosomes results in the gradual degradation of long-lived cytoplasmic proteins.

Additional resources

Protein Degradation


Cell Meter™ Autophagy Fluorescence Imaging Kit