The shortened replicative life span of prohibitin mutants of yeast appears to be due to defective mitochondrial segregation in old mother cells.
Prohibitin proteins have been implicated in cell proliferation, aging, respiratory chain assembly and the maintenance of mitochondrial integrity. The prohibitins of Saccharomyces cerevisiae, Phb1 and Phb2, have strong sequence similarity with their human counterparts prohibitin and BAP37, making yeast a good model organism in which to study prohibitin function. Both yeast and mammalian prohibitins form high-molecular-weight complexes (Phb1/2 or prohibitin/BAP37, respectively) in the inner mitochondrial membrane. Expression of prohibitins declines with senescence, both in mammalian fibroblasts and in yeast. With a total loss of prohibitins, the replicative (budding) life span of yeast is reduced, whilst the chronological life span (the survival of stationary cells over time) is relatively unaffected. This effect of prohibitin loss on the replicative life span is still apparent in the absence of an assembled respiratory chain. It also does not reflect the production of extrachromosomal ribosomal DNA circles (ERCs), a genetic instability thought to be a major cause of replicative senescence in yeast. Examination of cells containing a mitochondrially targeted green fluorescent protein indicates this shortened life span is a reflection of defective mitochondrial segregation from the mother to the daughter in the old mother cells of phb mutant strains. Old mother phb mutant cells display highly aberrant mitochondrial morphology and, frequently, a delayed segregation of mitochondria to the daughter. They often arrest growth with their last bud strongly attached and with the mitochondria adjacent to the septum between the mother and the daughter cell.
Piper
Peter W
PW
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK. piper@bsm.bioc.ucl.ac.uk
Jones
Gary W
GW
Bringloe
David
D
Harris
Nicholas
N
MacLean
Morag
M
Mollapour
Mehdi
M
D002455:Cell Division / Q000235:genetics*; D019069:Cell Respiration / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics*; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D004579:Electron Transport / Q000235:genetics; D008136:Longevity / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D000091402:Prohibitins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
D004275:DNA, Ribosomal; C000717328:PHB protein, human; C000717329:PHB1 protein, S cerevisiae; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011506:Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins