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Mitochondrial Sirt3 supports cell proliferation by regulating glutamine-dependent oxidation in renal cell carcinoma.

Authors
 Jieun Choi  ;  Eunjin Koh  ;  Yu Shin Lee  ;  Hyun-Woo Lee  ;  Hyeok Gu Kang  ;  Young Eun Yoon  ;  Woong Kyu Han  ;  Kyung Hwa Choi  ;  Kyung-Sup Kim 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.474(3) : 547-553, 2016 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2016
MeSH
Carcinoma, Renal Cell/metabolism* ; Carcinoma, Renal Cell/pathology ; Cell Line, Tumor ; Cell Proliferation* ; Gene Expression Regulation, Neoplastic ; Glutamine/metabolism* ; Humans ; Kidney Neoplasms/metabolism* ; Kidney Neoplasms/pathology ; Mitochondria/metabolism ; Mitochondria/pathology ; Mitochondrial Proteins/metabolism* ; Oxidation-Reduction ; Sirtuin 3/metabolism* ; Tumor Cells, Cultured
Keywords
Glutamate dehydrogenase ; Mitochondrial oxidation ; Renal cell carcinoma ; Sirt3
Abstract
Clear cell renal carcinoma (RCC), the most common malignancy arising in the adult kidney, exhibits increased aerobic glycolysis and low mitochondrial respiration due to von Hippel-Lindau gene defects and constitutive hypoxia-inducible factor-α expression. Sirt3 is a major mitochondrial deacetylase that mediates various types of energy metabolism. However, the role of Sirt3 as a tumor suppressor or oncogene in cancer depends on cell types. We show increased Sirt3 expression in the mitochondrial fraction of human RCC tissues. Sirt3 depletion by lentiviral short-hairpin RNA, as well as the stable expression of the inactive mutant of Sirt3, inhibited cell proliferation and tumor growth in xenograft nude mice, respectively. Furthermore, mitochondrial pyruvate, which was used for oxidation in RCC, might be derived from glutamine, but not from glucose and cytosolic pyruvate, due to depletion of mitochondrial pyruvate carrier and the relatively high expression of malic enzyme 2. Depletion of Sirt3 suppressed glutamate dehydrogenase activity, leading to impaired mitochondrial oxygen consumption. Our findings suggest that Sirt3 plays a tumor-progressive role in human RCC by regulating glutamine-derived mitochondrial respiration, particularly in cells where mitochondrial usage of cytosolic pyruvate is severely compromised.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X16306313
DOI
10.1016/j.bbrc.2016.04.117
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Koh, Eun Jin(고은진) ORCID logo https://orcid.org/0000-0001-8967-6266
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Yoon, Young Eun(윤영은)
Han, Woong Kyu(한웅규) ORCID logo https://orcid.org/0000-0002-2527-4046
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146880
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