{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T14:24:22Z","timestamp":1787149462608,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005969","name":"University of Bologna","doi-asserted-by":"publisher","award":["RFO 2025"],"award-info":[{"award-number":["RFO 2025"]}],"id":[{"id":"10.13039\/501100005969","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RFO 2025"],"award-info":[{"award-number":["RFO 2025"]}],"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Oxidative stress is closely associated with mitochondrial dysfunction and contributes to the development of several human diseases. Among antioxidant compounds, ASC and NAC are widely used for their cytoprotective and redox-regulating properties; however, their direct effects on specific aspects of mitochondrial bioenergetics are only partially characterized. In the present study, we investigated the effects of ASC and NAC, individually and combined, on Mg2+-dependent F1FO-ATPase hydrolysis, mitochondrial free thiol content and respiration in isolated swine heart mitochondria. ASC significantly stimulated F1FO-ATPase activity in a concentration-dependent manner, whereas kinetic analysis indicated a mixed uncompetitive activation mechanism. In contrast, NAC alone did not significantly affect F1FO-ATPase activity but abolished the stimulatory effect of ASC when the two compounds were combined. Both ASC and NAC increased mitochondrial free thiol content, although no change was observed under combined treatment conditions. Mitochondrial oxygen consumption analysis revealed substrate-dependent effects of the two antioxidants on electron transport. Overall, ASC and NAC exerted distinct direct actions on isolated mitochondria, and their combination did not produce additive or synergistic effects. These findings provide new insights into the direct modulation of mitochondrial function by antioxidant compounds and may contribute to expanding understanding of their potential therapeutic and dietary supplement applications, particularly when combined.<\/jats:p>","DOI":"10.3390\/biology15161360","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:10:24Z","timestamp":1786374624000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redox-Dependent Modulation of Cardiac Mitochondrial F1FO-ATPase and Respiratory Function by N-Acetylcysteine and Sodium Ascorbate"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9462-0051","authenticated-orcid":false,"given":"Antonia","family":"Cugliari","sequence":"first","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Algieri","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Health and Health Professions, Link University, 00118 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2650-7034","authenticated-orcid":false,"given":"Patrycja A.","family":"Glogowski","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Unit, Heart, Chest and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-8727","authenticated-orcid":false,"given":"Fabiana","family":"Trombetti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Buscaroli","sequence":"additional","affiliation":[{"name":"Mitochon Srl, 40064 San Lazzaro di Savena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela","family":"Fabbri","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ettore","family":"Federici","sequence":"additional","affiliation":[{"name":"Mitochon Srl, 40064 San Lazzaro di Savena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-7158","authenticated-orcid":false,"given":"Salvatore","family":"Nesci","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101674","DOI":"10.1016\/j.redox.2020.101674","article-title":"Mitochondrial Electron Transport Chain: Oxidative Phosphorylation, Oxidant Production, and Methods of Measurement","volume":"37","author":"Braganza","year":"2020","journal-title":"Redox Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1042\/BST20210460","article-title":"Regulation and Functional Role of the Electron Transport Chain Supercomplexes","volume":"49","author":"Cogliati","year":"2021","journal-title":"Biochem. 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