The prohibitin family of mitochondrial proteins regulate replicative lifespan.

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 [5], and yeast RAS2, which controls the response to ultraviolet irradiation and other stresses [3]. Another gene postulated to effect 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.

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
Volume: 7
Issue: 8
Pages: 607-10
Date: Aug. 1, 1997
PMID: 9259555
Select reference article to upload


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.

Update (Admin) | Auto-Update

Comment on This Data Unit