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Coordinated Upregulation of Mitochondrial Biogenesis and Autophagy in Breast Cancer Cells: The Role of Dynamin Related Protein-1 and Implication for Breast Cancer Treatment

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dc.contributor.authorZou, Pengen
dc.contributor.authorLiu, Longhuaen
dc.contributor.authorZheng, Louise D.en
dc.contributor.authorPayne, Kyle K.en
dc.contributor.authorManjili, Masoud H.en
dc.contributor.authorIdowu, Michael O.en
dc.contributor.authorZhang, Jinfengen
dc.contributor.authorSchmelz, Eva M.en
dc.contributor.authorCheng, Zhiyongen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessioned2017-09-18T09:34:32Zen
dc.date.available2017-09-18T09:34:32Zen
dc.date.issued2016-09-26en
dc.date.updated2017-09-18T09:34:32Zen
dc.description.abstractOveractive mitochondrial fission was shown to promote cell transformation and tumor growth. It remains elusive how mitochondrial quality is regulated in such conditions. Here, we show that upregulation of mitochondrial fission protein, dynamin related protein-1 (Drp1), was accompanied with increased mitochondrial biogenesis markers (PGC1α, NRF1, and Tfam) in breast cancer cells. However, mitochondrial number was reduced, which was associated with lower mitochondrial oxidative capacity in breast cancer cells. This contrast might be owing to enhanced mitochondrial turnover through autophagy, because an increased population of autophagic vacuoles engulfing mitochondria was observed in the cancer cells. Consistently, BNIP3 (a mitochondrial autophagy marker) and autophagic flux were significantly upregulated, indicative of augmented mitochondrial autophagy (mitophagy). The upregulation of Drp1 and BNIP3 was also observed in vivo (human breast carcinomas). Importantly, inhibition of Drp1 significantly suppressed mitochondrial autophagy, metabolic reprogramming, and cancer cell viability. Together, this study reveals coordinated increase of mitochondrial biogenesis and mitophagy in which Drp1 plays a central role regulating breast cancer cell metabolism and survival. Given the emerging evidence of PGC1α contributing to tumor growth, it will be of critical importance to target both mitochondrial biogenesis and mitophagy for effective cancer therapeutics.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationPeng Zou, Longhua Liu, Louise D. Zheng, et al., “Coordinated Upregulation of Mitochondrial Biogenesis and Autophagy in Breast Cancer Cells: The Role of Dynamin Related Protein-1 and Implication for Breast Cancer Treatment,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 4085727, 10 pages, 2016. doi:10.1155/2016/4085727en
dc.identifier.doihttps://doi.org/10.1155/2016/4085727en
dc.identifier.urihttp://hdl.handle.net/10919/78926en
dc.language.isoenen
dc.publisherHindawien
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderCopyright © 2016 Peng Zou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleCoordinated Upregulation of Mitochondrial Biogenesis and Autophagy in Breast Cancer Cells: The Role of Dynamin Related Protein-1 and Implication for Breast Cancer Treatmenten
dc.title.serialOxidative Medicine and Cellular Longevityen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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