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The regulation of mitochondria\u2010related pathways, such as aerobic respiration, is thought to be mediated by SESN2, but the underlying mechanisms are not fully understood. Here, we characterized mitochondria in\n                    <jats:italic>Sesn2<\/jats:italic>\n                    \u2010knockdown myoblasts under physiological conditions using oxygen consumption rate measurements, fluorescence microscopy, and protein content analysis. We discovered that SESN2 is essential for sustaining oxidative phosphorylation and maintaining the mitochondrial network organization. SESN2 loss diminished ATP production, decreased the levels of nuclear\u2010 and mitochondrial\u2010encoded complex IV subunits, and increased superoxide generation. Moreover, the assessment of mitochondrial distribution in\n                    <jats:italic>Sesn2<\/jats:italic>\n                    \u2010knockdown cells revealed a more fragmented network. This was associated with an increased ratio of short to long optic atrophy 1 (OPA1) forms. Remarkably, disruption of mitochondrial signaling suppressed cellular proliferation and altered both cell and nuclear morphology. In summary, our findings suggest that SESN2 plays an important role in maintaining cellular homeostasis, partly through its impact on mitochondrial function.\n                  <\/jats:p>","DOI":"10.1111\/febs.70497","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:51:08Z","timestamp":1773924668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oxidative phosphorylation and mitochondrial dynamics are regulated by Sestrin2 to maintain cellular function"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9666-4594","authenticated-orcid":false,"given":"Ivo F.","family":"Machado","sequence":"first","affiliation":[{"name":"CNC\u2010UC \u2013 Center for Neuroscience and Cell Biology University of Coimbra  Coimbra Portugal"},{"name":"CiBB \u2013 Center for Innovative Biomedicine and Biotechnology University of Coimbra  Coimbra Portugal"},{"name":"Institute of Interdisciplinary Research, Doctoral Program in Experimental Biology and Biomedicine (PDBEB) University of Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos M.","family":"Palmeira","sequence":"additional","affiliation":[{"name":"CNC\u2010UC \u2013 Center for Neuroscience and Cell Biology University of Coimbra  Coimbra Portugal"},{"name":"CiBB \u2013 Center for Innovative Biomedicine and Biotechnology University of Coimbra  Coimbra Portugal"},{"name":"Department of Life Sciences University of Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-9630","authenticated-orcid":false,"given":"Anabela P.","family":"Rolo","sequence":"additional","affiliation":[{"name":"CNC\u2010UC \u2013 Center for Neuroscience and Cell Biology University of Coimbra  Coimbra Portugal"},{"name":"CiBB \u2013 Center for Innovative Biomedicine and Biotechnology University of Coimbra  Coimbra Portugal"},{"name":"Department of Life Sciences University of Coimbra  Coimbra 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