Bengaluru, December 18, 2025 — Scientists at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) have discovered a critical regulatory mechanism in autophagy, the cellular “self-eating” process essential for removing damaged proteins and fighting infections. By identifying a new role for the exocyst complex—a group of eight proteins previously thought to only manage molecule transport—researchers have found the “missing link” in how cells manufacture autophagosomes, or cellular “trash bags.” This breakthrough, published in the Proceedings of the National Academy of Sciences (PNAS), provides a foundational roadmap for developing targeted therapies for Alzheimer’s, Parkinson’s, and various cancers where cellular waste management systems often fail.
The study, led by Professor Ravi Manjithaya, utilized yeast cells to demonstrate that seven out of the eight proteins in the exocyst complex are vital for “growing” the autophagosome so it can completely engulf cellular waste. Without this complex, the cell’s waste-processing factory either grinds to a halt or produces non-functional machinery, leading to the accumulation of toxic protein aggregates. This is particularly devastating for long-lived cells like neurons, which cannot easily regenerate. In diseases such as Huntington’s and Alzheimer’s, this disruption leads to cognitive decline, while in cancer, the process acts as a double-edged sword—initially suppressing tumors by maintaining genome integrity, but sometimes being hijacked by advanced cancer cells to survive harsh environments.
By uncovering how the exocyst complex facilitates the early steps of autophagosome biogenesis, the JNCASR team has opened up new avenues for “precision modulation” of the autophagy pathway. Future therapeutic strategies could involve drugs that restore the bag-making capability of cells in neurodegenerative cases or inhibit the process where cancer cells have co-opted it for their own growth. This research underscores the importance of fundamental cell biology in solving complex human health challenges, positioning India at the forefront of innovative molecular medicine and age-related disease research.
