{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:03:13Z","timestamp":1784728993878,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>\n                    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 the vacuole structure and function in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    as the vacuole plays a crucial role in handling oxidative stress-induced misfolded proteins. Our results indicated that CSE exposure causes transient vacuolar fragmentation peaking at 0.5\u00a0h, which correlates with reduced protein misfolding and improved cell survival. However, excessive fragmentation or vacuolar fusion sensitizes cells toward CSE-mediated cellular toxicity. To understand the underlying mechanism, this study provides the evidence of the involvement of PI(3,5)P2-Mediated signaling and phospholipase-driven remodeling of lipid moieties and suggests a role for mitochondrial function in CSE-mediated vacuolar fragmentation. Prolonged exposure to CSE impairs mitochondrial function and thus disrupts fragmentation, the adaptive survival strategy against cigarette smoke (CS). It results in proteostasis collapse, a characteristic shared by many inflammatory and degenerative disorders. Together, this study reveals a previously unrecognized cellular protection mechanism induced by CS and suggests avenues for further investigation for mitigating CS-mediated diseases.\n                  <\/jats:p>","DOI":"10.3389\/ftox.2026.1835170","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:17:01Z","timestamp":1784726221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Treatment of Saccharomyces cerevisiae with cigarette smoke extract causes vacuolar fragmentation to combat cigarette smoke-induced cellular toxicity"],"prefix":"10.3389","volume":"8","author":[{"given":"Aditya","family":"Shukla","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Calcutta","place":["Kolkata, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srimonti","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bose Institute","place":["Kolkata, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok Kumar","family":"Sil","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Calcutta","place":["Kolkata, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S0092-8674(00)80913-9","article-title":"Signaling via mitogen-activated protein kinase kinase (MEK1) is required for golgi fragmentation during mitosis","volume":"92","author":"Acharya","year":"1998","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/j.bbamcr.2019.02.011","article-title":"The vacuolar shapes of ageing: from function to morphology","volume":"1866","author":"Aufschnaiter","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3873","DOI":"10.1091\/mbc.E07-03-0222","article-title":"Role of the V-ATPase in regulation of the vacuolar fission\u2013fusion equilibrium","volume":"18","author":"Baars","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/13014","article-title":"The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast","volume":"1","author":"Bleazard","year":"1999","journal-title":"Nat. Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1139\/o59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1083\/jcb.200111009","article-title":"Osmotic stress\u2013induced increase of phosphatidylinositol 3,5-bisphosphate requires Vac14p, an activator of the lipid kinase Fab1p","volume":"156","author":"Bonangelino","year":"2002","journal-title":"J. Cell Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1034\/j.1600-0854.2000.010804.x","article-title":"Greasing membrane fusion and fission machineries","volume":"1","author":"Burger","year":"2000","journal-title":"Traffic"},{"key":"B8","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.cub.2020.10.051","article-title":"TORC1 determines Fab1 lipid kinase function at signaling endosomes and vacuoles","volume":"31","author":"Chen","year":"2021","journal-title":"Curr. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"27590","DOI":"10.1074\/jbc.274.39.27590","article-title":"Oxidative stress and iron are implicated in fragmenting vacuoles of Saccharomyces cerevisiae lacking Cu,Zn-superoxide dismutase","volume":"274","author":"Corson","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/36529","article-title":"Osmotic stress activates phosphatidylinositol-3,5-bisphosphate synthesis","volume":"390","author":"Dove","year":"1997","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"14241","DOI":"10.1074\/jbc.RA119.009460","article-title":"Autophagy activation promotes clearance of \u03b1-synuclein inclusions in fibril-seeded human neural cells","volume":"294","author":"Gao","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1007\/s11095-007-9516-9","article-title":"Extrinsic fluorescent dyes as tools for protein characterization","volume":"25","author":"Hawe","year":"2008","journal-title":"Pharm. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1016\/j.cub.2023.02.067","article-title":"Lipid peroxidation increases membrane tension, Piezo1 gating, and cation permeability to execute ferroptosis","volume":"33","author":"Hirata","year":"2023","journal-title":"Curr. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"523","DOI":"10.3390\/jof7070523","article-title":"Oxidative stress causes vacuolar fragmentation in the human fungal pathogen Cryptococcus neoformans","volume":"7","author":"Kim","year":"2021","journal-title":"J. Fungi"},{"key":"B15","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1128\/mr.54.3.266-292.1990","article-title":"The fungal vacuole: composition, function, and biogenesis","volume":"54","author":"Klionsky","year":"1990","journal-title":"Microbiol. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3994","DOI":"10.1242\/jcs.03149","article-title":"Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in Saccharomyces cerevisiae","volume":"119","author":"Kuravi","year":"2006","journal-title":"J. Cell Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3540","DOI":"10.1091\/mbc.E10-06-0483","article-title":"The sodium\/proton exchanger NHE8 regulates late endosomal morphology and function","volume":"21","author":"Lawrence","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/cc3992","article-title":"Reactive oxygen species: toxic molecules or spark of life?","volume":"10","author":"Magder","year":"2006","journal-title":"Crit. Care"},{"key":"B19","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.toxlet.2020.12.008","article-title":"Cigarette smoke affects ESCRT-Mediated vacuolar activity in Saccharomyces cerevisiae","volume":"338","author":"Maiti","year":"2021","journal-title":"Toxicol. Lett."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4684","DOI":"10.1073\/pnas.1720644115","article-title":"Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor","volume":"115","author":"Malia","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B21","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/372475a0","article-title":"Protein disaggregation mediated by heat-shock protein Hsp104","volume":"372","author":"Parsell","year":"1994","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.jgg.2012.03.004","article-title":"V-ATPase, ScNhx1p and yeast vacuole fusion","volume":"39","author":"Qiu","year":"2012","journal-title":"J. Genet. Genomics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1091\/mbc.3.12.1389","article-title":"Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants","volume":"3","author":"Raymond","year":"1992","journal-title":"Mol. Biol. Cell"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1201\/9781420078848","volume-title":"The Chemical Components of Tobacco and Tobacco Smoke","author":"Rodgman","year":"2008"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.3390\/antiox12091732","article-title":"Cigarette smoke-induced reactive oxygen species formation: a concise review","volume":"12","author":"Seo","year":"2023","journal-title":"Antioxidants"},{"key":"B26","doi-asserted-by":"publisher","first-page":"tfaf127","DOI":"10.1093\/toxres\/tfaf127","article-title":"Cigarette smoke impairs the endocytotic process in Saccharomyces cerevisiae","volume":"14","author":"Shukla","year":"2025","journal-title":"Toxicol. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"4618","DOI":"10.1091\/mbc.E15-07-0477","article-title":"Target of rapamycin signaling mediates vacuolar fission caused by endoplasmic reticulum stress in Saccharomyces cerevisiae","volume":"26","author":"Stauffer","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.bbrc.2022.04.080","article-title":"Vacuolar fragmentation promotes fluxes of microautophagy and micronucleophagy but not of macroautophagy","volume":"614","author":"Takuma","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B29","first-page":"1","article-title":"The effects of cigarette smoking on intraocular pressure and arterial blood pressure of normotensive young Nigerian Male adults","volume":"22","author":"Timothy","year":"2007","journal-title":"Niger. J. Physiol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1083\/jcb.128.5.779","article-title":"A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast","volume":"128","author":"Vida","year":"1995","journal-title":"J. Cell Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e202209077","DOI":"10.1083\/jcb.202209077","article-title":"A PI(3,5)P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes","volume":"222","author":"Vines","year":"2023","journal-title":"J. Cell Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1513\/pats.200809-100TH","article-title":"Smoking and lung cancer: the role of inflammation","volume":"5","author":"Walser","year":"2008","journal-title":"Proc. Am. Thorac. Soc."},{"key":"B33","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1083\/jcb.139.3.665","article-title":"Homotypic lysosome fusion in macrophages: analysis using an in vitro assay","volume":"139","author":"Ward","year":"1997","journal-title":"J. Cell Biol."},{"key":"B34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/978-1-59745-198-7_2","article-title":"The lowry method for protein quantitation","volume-title":"The Protein Protocols Handbook","author":"Waterborg","year":"2009"},{"key":"B35","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1146\/annurev.genet.37.050503.090845","article-title":"Yeast vacuole inheritance and dynamics","volume":"37","author":"Weisman","year":"2003","journal-title":"Annu. Rev. Genet."},{"key":"B36","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nrm1892","article-title":"Organelles on the move: insights from yeast vacuole inheritance","volume":"7","author":"Weisman","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1002\/1873-3468.13563","article-title":"Phosphatidic acid in membrane rearrangements","volume":"593","author":"Zhukovsky","year":"2019","journal-title":"FEBS Lett."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3438","DOI":"10.1091\/mbc.E12-03-0204","article-title":"Yeast vacuoles fragment in an asymmetrical two-phase process with distinct protein requirements","volume":"23","author":"Zieger","year":"2012","journal-title":"Mol. Biol. Cell"}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1835170\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:17:03Z","timestamp":1784726223000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1835170\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":38,"alternative-id":["10.3389\/ftox.2026.1835170"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2026.1835170","relation":{},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"article-number":"1835170"}}