Coordinated Upregulation of Mitochondrial Biogenesis and Autophagy in Breast Cancer Cells: The Role of Dynamin Related Protein-1 and Implication for Breast Cancer Treatment
Joint Authors
Idowu, Michael
Cheng, Zhiyong
Zou, Peng
Liu, Longhua
Zheng, Louise D.
Payne, Kyle K.
Zhang, Jinfeng
Schmelz, Eva M.
Manjili, Masoud H.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-09-26
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Overactive 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.
American Psychological Association (APA)
Zou, Peng& Liu, Longhua& Zheng, Louise D.& Payne, Kyle K.& Manjili, Masoud H.& Idowu, Michael…[et al.]. 2016. 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, no. 2016, pp.1-10.
https://search.emarefa.net/detail/BIM-1113900
Modern Language Association (MLA)
Zou, Peng…[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 No. 2016 (2016), pp.1-10.
https://search.emarefa.net/detail/BIM-1113900
American Medical Association (AMA)
Zou, Peng& Liu, Longhua& Zheng, Louise D.& Payne, Kyle K.& Manjili, Masoud H.& Idowu, Michael…[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. 2016. Vol. 2016, no. 2016, pp.1-10.
https://search.emarefa.net/detail/BIM-1113900
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1113900