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bioRxiv · 10.64898/2026.01.30.702977

Treatment of Saccharomyces cerevisiae with cigarette smoke extract causes vacuolar fragmentation to combat cigarette smoke-induced cellular toxicity

Shukla, A.·Sarkar, S.·Sil, A. K.
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Abstract

Exposure to cigarette smoke is one of the major risk factors for developing various diseases such as chronic obstructive pulmonary disease (COPD), cardiovascular disorders, and cancer mediated via cellular oxidative stress and organelle dysfunction. To this end, the current study investigated how cigarette smoke extract (CSE) affects vacuole structure and function in Saccharomyces cerevisiae, as vacuole plays a crucial role in handling oxidative stress-induced misfolded proteins. Our results showed that CSE exposure causes transient vacuolar fragmentation up to 1 h to increase its surface area to facilitate microautophagy in clearing CSE-mediated misfolded protein and promoting cell survival. However, excessive fragmentation or vacuolar fusion sensitizes cells towards CSE-mediated cellular toxicity. Towards understanding the underlying mechanism, the current study demonstrated the involvement of PI3P and PI (3,5) P2-mediated signaling and phospholipase-driven remodeling of lipid moieties. Moreover, the current study also showed the importance of mitochondrial activity in CSE-mediated vacuolar fragmentation. Prolonged exposure to CSE impairs mitochondrial function and thus disrupts fragmentation, the adaptive survival strategy against CS. It results in proteostasis collapse, which is a characteristic shared by many inflammatory and degenerative disorders. Taken together, the current study reveals a previously unrecognized cellular protection mechanism induced by cigarette smoke and highlights potential therapeutic targets for mitigating CS-mediated diseases

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Shukla, A., Sarkar, S., Sil, A. K.. 2026-02-02. Treatment of Saccharomyces cerevisiae with cigarette smoke extract causes vacuolar fragmentation to combat cigarette smoke-induced cellular toxicity. https://doi.org/10.64898/2026.01.30.702977

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