The prohibitin family of mitochondrial proteins regulate replicative lifespan
The prohibitin family of mitochondrial proteins regulate replicative lifespan
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DOI：
10.1016/s0960-9822(06)00261-2
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发表时间：
1997-08-01
期刊：
影响因子：
9.2
通讯作者：
Hall, PA
中科院分区：
文献类型：
--
作者：
Coates, PJ;Jamieson, DJ;Hall, PA
细胞衰老由多种因素决定，包括代谢的遗传调节以及对内源性和外源性应激的反应[1-4]。最近的研究表明，在酵母和秀丽隐杆线虫中，有有限数量的基因产物可以延长寿命[2-4];另一个被认为影响衰老的基因是PHB 1，它是prohibitin的酵母同源物[3]，一种最初被鉴定为生长停滞和肿瘤抑制的潜在调节因子的啮齿动物基因[6-8]，在哺乳动物[9]、果蝇[10]、C.第二种哺乳动物基因，编码BAP 37，一种与prohibitin具有序列相似性的蛋白质，被认为参与淋巴细胞功能[9]。在这里，我们表明核编码的哺乳动物prohibitin和BAP 37蛋白存在于线粒体中，共表达，并且彼此物理相互作用。酿酒酵母同系物的缺失，PHB 1和PHB 2导致细胞复制寿命的缩短和线粒体膜电位的缺陷。我们的观察结果突出了细胞代谢效率与衰老过程之间的关系，并为其进化保守性提供了证据。
Cellular senescence is determined by multiple factors, including the genetic regulation of metabolism and responses to endogenous and exogenous stresses [1-4]. Recent studies implicate a limited number of gene products in elongating lifespan in yeast and Caenorhabditis elegans [2-4]; these include the C. elegans gene clk-1, a central regulator of metabolism [5], and yeast RAS2, which controls the response to ultraviolet irradiation and other stresses [3], Another gene postulated to affect senescence is PHB1, the yeast homologue of prohibitin [3], a rodent gene initially identified as a potential regulator of growth arrest and tumour suppressor [6-8], Highly conserved prohibitin homologues have been identified in mammals [9], Drosophila [10], C. elegans [9], plants [11] and yeast, A second mammalian gene, encoding BAP37, a protein with sequence similarity to prohibitin, is thought to be involved in lymphocyte function [9], Here, we show that the nuclear encoded mammalian prohibitin and BAP37 proteins are present in mitochondria, are co-expressed, and interact physically with each other, Deletion of the Saccharomyces cerevisiae homologues, PHB1 and PHB2, results in a decreased replicative lifespan and a defect in mitochondrial membrane potential, Our observations highlight the relationship between the metabolic efficiency of cells and the ageing process, and provide evidence for its evolutionary conservation.