Indian researchers have discovered a new element in autophagy, the body’s natural self-cleansing process through the removal of dead or damaged cells, which could help develop therapeutic strategies for diseases like Alzheimer’s, Parkinson’s and cancer.
Identification of key players in the early steps of autophagosome biogenesis, a key process in which the cells create a double-membrane sack that captures and isolates cellular debris, pathogens or damaged organelles for recycling, can lay the foundations for modulating the pathway for finding interventions in such diseases.
When a cell fails to clear waste, its health suffers, especially in long-lived neurons. The autophagy pathway, which removes damaged material and defends against infections, is disrupted in diseases like Alzheimer’s and Huntington’s.
Autophagy also has dual roles in cancer, by preventing it early on but supporting tumour growth later. Autophagy acts as tumour suppressor by maintaining genome integrity and cellular homeostasis by clearing cellular junk, but it is also a double-edged sword as certain types of cancer cells hijack autophagy for their own survival and propagation. Understanding its regulation is crucial for the development of effective therapies, according to information shared by the Ministry of Science and Technology on Friday.
Researchers from Jawaharlal Nehru Centre for Advanced Scientific Research found that a group of proteins called the ‘exocyst complex’, which normally helps move important molecules to the cell surface, also plays a key role in autophagy.
This complex comprises a set of eight proteins, out of which seven are required to help the cell grow the sack so that it can completely wrap up the waste. When this complex goes missing, the cell’s sack-making capacity stops working properly and even starts to produce faulty or non-functional matter.
The researchers led by Prof Ravi Manjithaya used simple yeast cells to elucidate the formation of autophagosomes, thereby providing insights into how this vital process operates in higher organisms.
“The study significantly enhances our understanding of membrane expansion during autophagy by decoding the role of the tethering exocyst complex during the autophagosome biogenesis,” the researchers said.
“The findings have a broad impact on fundamentally understanding the conditions involved in maintaining cellular health and the dysregulation during diseases such as neuro-degeneration, cancer and aging,” they added. The study has been published in Proceedings of the National Academy of Sciences of the United States of America, a peer-reviewed multidisciplinary scientific journal.
The researchers elaborated upon the mechanism by which a protein complex exocyst, also contributes to the autophagy pathway, which is crucial for maintaining cellular health. “Since defects in autophagy are linked to several neurodegenerative diseases and cancers, the findings have opened new avenues for modulating this pathway to restore cellular balance and develop potential therapies,” the ministry said.
