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ID 115642
著者
Nowinski, Sara M. The University of Texas at Austin|The University of Utah
Solmonson, Ashley The University of Texas at Austin
Rundhaug, Joyce E. University of Texas
Rho, Okkyung The University of Texas at Austin
Cho, Jiyoon The University of Texas at Austin
Lago, Cory U. National Institutes of Health
Riley, Christopher L. The University of Texas at Austin
Lee, Sunhee The University of Texas at Austin
Kohno, Shohei The University of Texas at Austin
Dao, Christine K. The University of Texas at Austin
Bratton, Shawn B. University of Texas
Wright, Casey W. The University of Texas at Austin
Fischer, Susan M. University of Texas
DiGiovanni, John The University of Texas at Austin
Mills, Edward M. The University of Texas at Austin
資料タイプ
学術雑誌論文
抄録
To support growth, tumour cells reprogramme their metabolism to simultaneously upregulate macromolecular biosynthesis while maintaining energy production. Uncoupling proteins (UCPs) oppose this phenotype by inducing futile mitochondrial respiration that is uncoupled from ATP synthesis, resulting in nutrient wasting. Here using a UCP3 transgene targeted to the basal epidermis, we show that forced mitochondrial uncoupling inhibits skin carcinogenesis by blocking Akt activation. Similarly, Akt activation is markedly inhibited in UCP3 overexpressing primary human keratinocytes. Mechanistic studies reveal that uncoupling increases fatty acid oxidation and membrane phospholipid catabolism, and impairs recruitment of Akt to the plasma membrane. Overexpression of Akt overcomes metabolic regulation by UCP3, rescuing carcinogenesis. These findings demonstrate that mitochondrial uncoupling is an effective strategy to limit proliferation and tumorigenesis through inhibition of Akt, and illuminate a novel mechanism of crosstalk between mitochondrial metabolism and growth signalling.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
6
開始ページ
8137
発行日
2015-08-27
権利情報
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系