{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:05:17Z","timestamp":1791493517019,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T00:00:00Z","timestamp":1578096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KWF Young Investigator","award":["No. 10140"],"award-info":[{"award-number":["No. 10140"]}]},{"name":"VIDI grant from the Netherlands Organization","award":["No. 91719300"],"award-info":[{"award-number":["No. 91719300"]}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["No. 114027003"],"award-info":[{"award-number":["No. 114027003"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["No. 201506100033"],"award-info":[{"award-number":["No. 201506100033"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metabolic reprogramming universally occurs in cancer. Mitochondria act as the hubs of bioenergetics and metabolism. The morphodynamics of mitochondria, comprised of fusion and fission processes, are closely associated with mitochondrial functions and are often dysregulated in cancer. In this study, we aim to investigate the mitochondrial morphodynamics and its functional consequences in human liver cancer. We observed excessive activation of mitochondrial fusion in tumor tissues from hepatocellular carcinoma (HCC) patients and in vitro cultured tumor organoids from cholangiocarcinoma (CCA). The knockdown of the fusion regulator genes, OPA1 (Optic atrophy 1) or MFN1 (Mitofusin 1), inhibited the fusion process in HCC cell lines and CCA tumor organoids. This resulted in inhibition of cell growth in vitro and tumor formation in vivo, after tumor cell engraftment in mice. This inhibitory effect is associated with the induction of cell apoptosis, but not related to cell cycle arrest. Genome-wide transcriptomic profiling revealed that the inhibition of fusion predominately affected cellular metabolic pathways. This was further confirmed by the blocking of mitochondrial fusion which attenuated oxygen consumption and cellular ATP production of tumor cells. In conclusion, increased mitochondrial fusion in liver cancer alters metabolism and fuels tumor cell growth.<\/jats:p>","DOI":"10.3390\/cells9010121","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T03:48:48Z","timestamp":1578282528000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Mitochondrial Fusion Via OPA1 and MFN1 Supports Liver Tumor Cell Metabolism and Growth"],"prefix":"10.3390","volume":"9","author":[{"given":"Meng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Hepatology, Beijing 302 Hospital, Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoshi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7848-3933","authenticated-orcid":false,"given":"Ruby","family":"Lieshout","sequence":"additional","affiliation":[{"name":"Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buyun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changbo","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, 3015 CE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9908-6673","authenticated-orcid":false,"given":"Monique M. 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