دورية أكاديمية
Mitochondrial fusion supports increased oxidative phosphorylation during cell proliferation
| العنوان: | Mitochondrial fusion supports increased oxidative phosphorylation during cell proliferation |
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| المؤلفون: | Cong-Hui Yao, Rencheng Wang, Yahui Wang, Che-Pei Kung, Jason D Weber, Gary J Patti |
| المصدر: | eLife, Vol 8 (2019) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | oxidative phosphorylation, mitochondrial fusion, cell proliferation, warburg effect, metabolism, cancer, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Proliferating cells often have increased glucose consumption and lactate excretion relative to the same cells in the quiescent state, a phenomenon known as the Warburg effect. Despite an increase in glycolysis, however, here we show that non-transformed mouse fibroblasts also increase oxidative phosphorylation (OXPHOS) by nearly two-fold and mitochondrial coupling efficiency by ~30% during proliferation. Both increases are supported by mitochondrial fusion. Impairing mitochondrial fusion by knocking down mitofusion-2 (Mfn2) was sufficient to attenuate proliferation, while overexpressing Mfn2 increased proliferation. Interestingly, impairing mitochondrial fusion decreased OXPHOS but did not deplete ATP levels. Instead, inhibition caused cells to transition from excreting aspartate to consuming it. Transforming fibroblasts with the Ras oncogene induced mitochondrial biogenesis, which further elevated OXPHOS. Notably, transformed fibroblasts continued to have elongated mitochondria and their proliferation remained sensitive to inhibition of Mfn2. Our results suggest that cell proliferation requires increased OXPHOS as supported by mitochondrial fusion. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/41351; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.41351 |
| URL الوصول: | https://doaj.org/article/e65f61cec7b345d382006736cb79f515 |
| رقم الأكسشن: | edsdoj.65f61cec7b345d382006736cb79f515 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.41351 |