Green D W, Grover G J
3-Dimensional Pharmaceuticals, Inc., Exton, PA 19341, USA.
Biochim Biophys Acta. 2000 May 31;1458(2-3):343-55. doi: 10.1016/s0005-2728(00)00085-2.
Recent studies on the IF(1) inhibitor protein of the mitochondrial F(1)F(0)-ATPase from molecular biochemistry to possible pathophysiological roles are reviewed. The apparent mechanism of IF(1) inhibition of F(1)F(0)-ATPase activity and the biophysical conditions that influence IF(1) activity are summarized. The amino acid sequences of human, bovine, rat and murine IF(1) are compared and domains and residues implicated in IF(1) function examined. Defining the minimal inhibitory sequence of IF(1) and the role of conserved histidines and conformational changes using peptides or recombinant IF(1) is reviewed. Luft's disease, a mitochondrial myopathy where IF(1) is absent, is described with respect to IF(1) relevance to mitochondrial bioenergetics and clinical observations. The possible pathophysiological role of IF(1) in conserving ATP under conditions where cells experience oxygen deprivation (tumor growth, myocardial ischemia) is evaluated. Finally, studies attempting to correlate IF(1) activity to ATP conservation in myocardial ischemic preconditioning are compared.
本文综述了近年来关于线粒体F(1)F(0)-ATP酶的IF(1)抑制蛋白从分子生物化学到可能的病理生理作用的研究。总结了IF(1)抑制F(1)F(0)-ATP酶活性的表观机制以及影响IF(1)活性的生物物理条件。比较了人、牛、大鼠和小鼠IF(1)的氨基酸序列，并研究了与IF(1)功能相关的结构域和残基。综述了使用肽或重组IF(1)确定IF(1)的最小抑制序列以及保守组氨酸和构象变化的作用。描述了与IF(1)相关的线粒体生物能量学和临床观察的卢夫特病，这是一种缺乏IF(1)的线粒体肌病。评估了IF(1)在细胞缺氧条件下（肿瘤生长、心肌缺血）保存ATP的可能病理生理作用。最后，比较了试图将IF(1)活性与心肌缺血预处理中的ATP保存相关联的研究。
