Researchers from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) under the Department of Science and Technology have identified a previously unrecognised role for a group of proteins in the process cells use to clear damaged components, defend against infections and maintain health, particularly in long‑lived cells like neurons.
This cellular cleanup process, known as autophagy, involves the formation of specialized structures called autophagosomes that engulf and remove unwanted material.
Scientists found that the exocyst complex, a set of eight proteins known for helping transport molecules to the cell surface, is also critical in the early stages of forming autophagosomes. Seven of the eight proteins are necessary for the cell to grow the membrane structures that wrap up cellular waste, and without this complex, the mechanism that builds these structures fails or becomes defective.
Autophagy is essential for removing damaged mitochondria and aggregates of proteins that can otherwise accumulate and disrupt cell function. When this self‑cleaning mechanism fails, it is linked to several serious conditions, including neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s, where long‑lived neurons are vulnerable, and to cancer, where autophagy can act in dual roles, helping suppress tumour development in early stages by maintaining genomic stability, and in later stages being utilised by cancer cells to survive and propagate.
The research team, led by Prof. Ravi Manjithaya, used yeast cells as a model to reveal how autophagosomes are formed, providing insights that apply to higher organisms. By elucidating the mechanism through which the exocyst complex contributes to the autophagy pathway, the study highlights a new piece of the biological puzzle that could be targeted to restore cellular balance when autophagy is disrupted.
These findings, published in the journal Proceedings of the National Academy of Sciences, point to potential strategies for developing therapeutic interventions for Alzheimer’s, Parkinson’s and cancer by modulating the autophagy pathway.
