Academic Journal
Prevention and regression of megamitochondria and steatosis by blocking mitochondrial fusion in the liver
| العنوان: | Prevention and regression of megamitochondria and steatosis by blocking mitochondrial fusion in the liver |
|---|---|
| المؤلفون: | Tatsuya Yamada, Daisuke Murata, David E. Kleiner, Robert Anders, Avi Z. Rosenberg, Jeffrey Kaplan, James P. Hamilton, Mariam Aghajan, Moshe Levi, Nae-Yuh Wang, Ted M. Dawson, Toru Yanagawa, Andrew F. Powers, Miho Iijima, Hiromi Sesaki |
| المصدر: | iScience, Vol 25, Iss 4, Pp 103996- (2022) |
| بيانات النشر: | Elsevier, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Science |
| مصطلحات موضوعية: | Hepatology, Cell biology, Science |
| الوصف: | Summary: Non-alcoholic steatohepatitis (NASH) is a most common chronic liver disease that is manifested by steatosis, inflammation, fibrosis, and tissue damage. Hepatocytes produce giant mitochondria termed megamitochondria in patients with NASH. It has been shown that gene knockout of OPA1, a mitochondrial dynamin-related GTPase that mediates mitochondrial fusion, prevents megamitochondria formation and liver damage in a NASH mouse model induced by a methionine-choline-deficient (MCD) diet. However, it is unknown whether blocking mitochondrial fusion mitigates NASH pathologies. Here, we acutely depleted OPA1 using antisense oligonucleotides in the NASH mouse model before or after megamitochondria formation. When OPA1 ASOs were applied at the disease onset, they effectively prevented megamitochondria formation and liver pathologies in the MCD model. Notably, even when applied after mice robustly developed NASH pathologies, OPA1 targeting effectively regressed megamitochondria and the disease phenotypes. Thus, our data show the efficacy of mitochondrial dynamics as a unique therapy for megamitochondria-associated liver disease. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2589-0042 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2589004222002668; https://doaj.org/toc/2589-0042 |
| DOI: | 10.1016/j.isci.2022.103996 |
| URL الوصول: | https://doaj.org/article/0fae080557bb4652bb50c5207550ede1 |
| رقم الانضمام: | edsdoj.0fae080557bb4652bb50c5207550ede1 |
| قاعدة البيانات: | Directory of Open Access Journals |
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