Scientists in Japan have used a novel technique to identify a protein complex degraded by autophagy that has a possible role in liver cancer.
Biomolecular condensates like p62 body have a role in cleansing cellular waste through ‘autophagy’, though much remains unknown about the constituents of these membrane-less organelles.
Associate Professor Hideaki Morishita, Juntendo University Graduate School of Medicine, said: “Our methods have a broad scope of potential applications that should lead to the discovery of currently uncharacterised phase separation-mediated cargoes in order to allow for a deeper understanding of selective autophagy and related diseases.”
The scientists developed a method that combines fluorescence-activated particle sorting (FAPS) and selective autophagy-deficient mouse tissues to identify several p62-body components, including a major subunit of the supramolecular protein complex, vault, which is likely linked with non-alcoholic steatohepatitis-derived hepatocellular carcinoma.
When these cellular components grow old or get damaged, they are digested by a process called autophagy. This process not only helps in the elimination of toxic waste, but also helps to deliver building blocks for the synthesis of new cellular macromolecules.
p62 protein forms a membrane-less cytosolic organelle called p62 body and helps in the selective removal of toxic cellular waste through autophagy. Regulated removal of unwanted proteins via selective autophagy of p62 bodies maintains cellular homeostasis. However, their compromised clearance leads to the accumulation of p62 and proteins inside p62 bodies, resulting in several diseases, such as hepatocellular carcinoma.
Professor Masaaki Komatsu, Juntendo University Graduate School of Medicine, added: “Our proteomic approach identified the contents of p62 bodies in detail and enabled us to determine the substrates of p62-mediated selective autophagy. This method can be applied to other cell types and tissues under several conditions, like stress and diseases.”