{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:44:15Z","timestamp":1778895855576,"version":"3.51.4"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Center of Semmelweis University","award":["STIA-OTKA 1283978\/IPK2020"],"award-info":[{"award-number":["STIA-OTKA 1283978\/IPK2020"]}]},{"name":"Semmelweis University 250+ PhD Excellence Grant","award":["EFOP-3.6.3-VEKOP-16-2017 00009"],"award-info":[{"award-number":["EFOP-3.6.3-VEKOP-16-2017 00009"]}]},{"name":"Bolyai J\u00e1nos Research Grant of the Hungarian Academy of Sciences"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Aim<\/jats:title>\n<jats:p>Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The CypD KO group displayed improved mitochondrial function, as both ATP production (P &lt; 0.001) and oxygen consumption (P &lt; 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor \u03b3 co-activator 1-\u03b1 (PGC1-\u03b1) was also elevated in the CypD KO group (P &lt; 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P &lt; 0.001).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0271606","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T17:47:28Z","timestamp":1657820848000},"page":"e0271606","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The effect of Cyclophilin D depletion on liver regeneration following associating liver partition and portal vein ligation for staged 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