{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:36:43Z","timestamp":1773391003608,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ebm-journal.org"],"crossmark-restriction":true},"short-container-title":["Exp. Biol. Med."],"abstract":"<jats:p>\n                    Oxidative stress is a primary driver of aging, necessitating robust cellular adaptation mechanisms. While peroxisomal \u03b2-oxidation and proteasomal degradation are known to influence stress responses, their functional crosstalk remains elusive. In this study, we show that\n                    <jats:italic>C. elegans acox-1.1<\/jats:italic>\n                    mutants, despite having a shortened lifespan under normal conditions, exhibit a paradoxical resistance to mild chronic oxidative stress (1\u00a0mM paraquat, PQ) compared to wild-type worms. This PQ-induced resistance in\n                    <jats:italic>acox-1.1<\/jats:italic>\n                    mutants was independent of the canonical SKN-1 pathway but required the peroxisomal catalase CTL-3. RNA-mediated knockdown of\n                    <jats:italic>ctl-3<\/jats:italic>\n                    largely abolished the stress resistance of\n                    <jats:italic>acox-1.1<\/jats:italic>\n                    mutants, leading to rapid mortality. Proteomic and biochemical analyses revealed that\n                    <jats:italic>acox-1.1<\/jats:italic>\n                    mutants possess reduced levels of PAS-5, a core 20S proteasome subunit, resulting in impaired proteasomal assembly and accumulation of ubiquitinated (Ub) substrates under basal conditions. Intriguingly, exposure to 1\u00a0mM PQ significantly reduced the Ub-smear in\n                    <jats:italic>acox-1.1<\/jats:italic>\n                    mutants, suggesting a metabolic shift where the cell prioritizes ROS scavenging over ATP-dependent protein degradation. Under oxidative stress,\n                    <jats:italic>acox-1.1<\/jats:italic>\n                    mutants bypass defective proteasomal machinery and redirect energy toward CTL-3-mediated antioxidant defense. This study identified a peroxisomal adaptation mechanism whereby reduced proteasome complexity, coupled with enhanced ROS-regulatory machinery, confers survival advantages under specific oxidative challenges.\n                  <\/jats:p>","DOI":"10.3389\/ebm.2026.10796","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:10:10Z","timestamp":1773382210000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced oxidative stress resilience in C. elegans acox-1.1 mutants through CTL-3 and proteasomal regulation"],"prefix":"10.3389","volume":"251","author":[{"given":"Woori","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine","place":["New York, NY, United States"]},{"name":"Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina","family":"Norman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology\/Oncology Division, Brody School of Medicine at East Carolina University","place":["Greenville, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myon Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology\/Oncology Division, Brody School of Medicine at East Carolina University","place":["Greenville, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/j.bbadis.2011.12.001","article-title":"Role of peroxisomes in ROS\/RNS-metabolism: implications for human disease","volume":"1822","author":"Fransen","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1016\/j.bbamcr.2006.09.006","article-title":"Peroxisomes and oxidative stress","volume":"1763","author":"Schrader","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1093\/mp\/ssu070","article-title":"Spatial H2O2 signaling specificity: H2O2 from chloroplasts and peroxisomes modulates the plant transcriptome differentially","volume":"7","author":"Sewelam","year":"2014","journal-title":"Mol Plant"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3296","DOI":"10.1093\/hmg\/ddt186","article-title":"Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy","volume":"22","author":"Lopez-Erauskin","year":"2013","journal-title":"Hum Molecular Genetics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.biochi.2013.07.026","article-title":"Peroxisomal metabolism and oxidative stress","volume":"98","author":"Nordgren","year":"2014","journal-title":"Biochimie"},{"key":"B6","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1089\/ars.2009.2996","article-title":"Peroxisomes are oxidative organelles","volume":"13","author":"Antonenkov","year":"2010","journal-title":"Antioxid and Redox Signaling"},{"key":"B7","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1104\/pp.106.078204","article-title":"Reactive oxygen species and reactive nitrogen species in peroxisomes. 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