Authors: Coates PJ; Jamieson DJ; Smart K; Prescott AR; Hall PA
Abstract: 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 cik-1, a central regulator of metabolism , and yeast RAS2, which controls the response to ultraviolet irradiation and other stresses . Another gene postulated to effect senescence is PHB1, the yeast homologue of prohibitin , 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 , Drosophila , C. elegans , plants  and yeast. A second mammalian gene, encoding BAP37, a protein with sequence similarity to prohibitin, is thought to be involved in lymphocyte function . 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.Keywords: Amino Acid Sequence; Animals; Cell Aging/genetics/*physiology; Humans; Mice; Mitochondria/genetics/*physiology; Molecular Sequence Data; Proteins/genetics/*physiology; *Repressor Proteins; Sequence Homology, Amino Acid
Journal: Current biology : CB
Date: Aug. 1, 1997
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Coates PJ, Jamieson DJ, Smart K, Prescott AR, Hall PA (1997) The prohibitin family of mitochondrial proteins regulate replicative lifespan. Current biology : CB 7: 607-10.