{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T05:20:59Z","timestamp":1765689659761,"version":"3.48.0"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT I.P.","award":["UID\/04050\/2025"],"award-info":[{"award-number":["UID\/04050\/2025"]}]},{"name":"FCT","award":["SFRH\/BD\/132070\/2017"],"award-info":[{"award-number":["SFRH\/BD\/132070\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The pro-apoptotic protein Bax is a key apoptosis regulator, as its activity is the main driver of mitochondrial outer membrane permeabilization. Bax is therefore tightly regulated, both by protein\u2013protein interactions and post-translational modifications, such as phosphorylation. Although less studied, N-terminal acetylation has also been implicated in Bax regulation: disruption of the NatB N-terminal acetyl transferase complex in both yeast and MEFs increases Bax mitochondrial localization, although increased translocation is not sufficient to trigger its activation. Using the well-established model of heterologous expression of human Bax in yeast, we further investigated its regulation by N-terminal acetylation. We found that the sensitivity of Bax-expressing cells to acetic acid is greatly enhanced in a strain lacking the yeast NatB catalytic subunit (Nat3p). We propose that the Bax-induced cell death process shifts to a regulated necrosis in this strain due to autophagy inhibition. Furthermore, we show that the protective role of Bcl-xL against acetic acid-induced cell death of Bax-expressing yeast cells requires Nat3p. We speculate that Nat3p modulates the function of pro-death and pro-survival proteins, ultimately affecting both the levels and mode of cell death. These findings may have implications for the development of novel therapeutic strategies targeting human diseases associated with cell death dysfunction.<\/jats:p>","DOI":"10.3390\/biom15121731","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T09:37:48Z","timestamp":1765532268000},"page":"1731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Yeast NatB Regulates Cell Death of Bax-Expressing Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-5357","authenticated-orcid":false,"given":"Joana P.","family":"Guedes","sequence":"first","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2659-4591","authenticated-orcid":false,"given":"Filipa","family":"Mendes","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0709-4204","authenticated-orcid":false,"given":"Beatriz O.","family":"Machado","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5792-1084","authenticated-orcid":false,"given":"St\u00e9phen","family":"Manon","sequence":"additional","affiliation":[{"name":"Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires, UMR5095, Centre National de Recherche Scientifique, Universit\u00e9 de Bordeaux, 33076 Bordeaux, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1423-1331","authenticated-orcid":false,"given":"Manuela","family":"C\u00f4rte-Real","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-9872","authenticated-orcid":false,"given":"Susana R.","family":"Chaves","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.molcel.2012.12.022","article-title":"Bax Exists in a Dynamic Equilibrium between the Cytosol and Mitochondria to Control Apoptotic Priming","volume":"49","author":"Schellenberg","year":"2013","journal-title":"Mol. 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