Loss of prohibitins, though it shortens the replicative life span of yeast cells undergoing division, does not shorten the chronological life span of G0-arrested cells.
Prohibitin proteins have been implicated in cell proliferation, ageing and the maintenance of mitochondrial integrity. The yeast prohibitins, Phb1p and Phb2p, are close in sequence to their two human counterparts, prohibitin and BAP37. Mutants of Saccharomyces cerevisiae that lack these prohibitins have a shortened replicative (budding) life span. Nevertheless, their chronological life span, measured as the survival of stationary phase (G0) cells over time, is essentially normal. Loss of prohibitins does not hypersensitise cells to their endogenous free radical production, though it does slightly increase their sensitivity to ethanol. It is unlikely, therefore, that the influences of prohibitins over replicative senescence involve free radicals, despite the evidence from many systems linking ageing to the long-term effects of oxidative stress. Yeast phb1 and phb2 mutants and also the phb1, phb2 double mutant, tend to lose respiration competence when in G0-arrest, indicating that nondividing cells lacking prohibitins have problems maintaining a functional mitochondrial electron transport chain. This may reflect an imbalance in the turnover of components of the respiratory chain in G0 cells, since the Phb1/2p complex is known to help stabilise these components. Such losses of respiratory function in G0-arrested cells are greater with the loss of Phb1p than with the loss of Phb2p, revealing the Phb1p null and Phb2p null phenotypes to be nonidentical.
Piper
Peter W
PW
Department of Biochemistry and Molecular Biology, University College London, Gower Street, WC1E 6BT, London, UK. piper@bsm.bioc.ucl.ac.uk
Bringloe
David
D
D002455:Cell Division; D018384:Oxidative Stress; D000091402:Prohibitins; D011506:Proteins / Q000502:physiology*; D012097:Repressor Proteins; D016192:Resting Phase, Cell Cycle; D012441:Saccharomyces cerevisiae / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins
C000717328:PHB protein, human; C000717329:PHB1 protein, S cerevisiae; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011506:Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins