Fatty Acid Flippase Activity of UCP2 Is Essential for Its Proton Transport in Mitochondria

	Fatty Acid Flippase Activity of UCP2 Is Essential for Its Proton Transport in Mitochondria
	Berardi, MJ; Chou, JJ
刊名	CELL METABOLISM
	2014
卷号	20 期号:3 页码:541-552
通讯作者	Chou, JJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.,james_chou@hms.harvard.edu
英文摘要	Modulation of cellular energy expenditure is fundamental to normal and pathological cell growth and differentiation. Mitochondria stores energy as a proton gradient across their inner membrane. Uncoupling proteins (UCPs) can dissipate the gradient to produce heat or regulate metabolite fluxes. UCP-mediated proton currents require fatty acids (FAs) and are blocked by nucleotides, but the molecular basis of these processes is unknown. We find, by nuclear magnetic resonance and functional mutagenesis, that UCP2 can bind FAs laterally through its peripheral site, and this intramembrane molecular recognition is essential for UCP2-catalyzed FA flipping across the membrane, which in turn is essential for proton translocation. The antagonist GDP binds inside the UCP2 cavity and perturbs its conformation, which can displace FA from the peripheral site as a mean of inhibiting proton currents. Our data provide a biophysical perspective of the intricate interplay of UCPs, FA, and nucleotides in determining proton fluxes in mitochondria.
学科主题	Cell Biology ; Endocrinology & Metabolism
类目[WOS]	Cell Biology ; Endocrinology & Metabolism
关键词[WOS]	BROWN ADIPOSE-TISSUE ; UNCOUPLING PROTEIN-2 ; OXIDATIVE-PHOSPHORYLATION ; ADP/ATP CARRIER ; BINDING-PROTEIN ; MECHANISM ; CELL ; ADIPOCYTES ; METABOLISM ; SUBSTRATE
收录类别	SCI
语种	英语
WOS记录号	WOS:000341402800017
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/155]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Berardi, MJ,Chou, JJ. Fatty Acid Flippase Activity of UCP2 Is Essential for Its Proton Transport in Mitochondria[J]. CELL METABOLISM,2014,20(3):541-552.
APA	Berardi, MJ,&Chou, JJ.(2014).Fatty Acid Flippase Activity of UCP2 Is Essential for Its Proton Transport in Mitochondria.CELL METABOLISM,20(3),541-552.
MLA	Berardi, MJ,et al."Fatty Acid Flippase Activity of UCP2 Is Essential for Its Proton Transport in Mitochondria".CELL METABOLISM 20.3(2014):541-552.