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 ha c been implicated in cell proliferation, ageing and the maintenance of mitochondrial integrity. The yeast prohibitins, Phb I p and Phb2p, are close in sequence to their two human counterparts, prohibitin and BAP37. Mutants of Saccharomyces cerevisiae that lack these prohibitins hake a shortened replicative (budding) life span. Nevertheless, their chronological life span, measured as the survival of stationary phase (G(0)) 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 phb 1 and phb2 mutants and also the phb1, phb2 double mutant, tend to lose respiration competence when in G(0)-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 or the respiratory chain in G(0), cells, since the Phb1/2p complex is known to help stabilise these components. Such losses or respiratory function in G(0)-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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.