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2003 | 50 | 4 |

Tytuł artykułu

Prohibitins and Ras2 protein cooperate in the maintenance of mitochondrial function during yeast aging

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
The yeast Saccharomyces cerevisiae has a finite replicative life span. Yeasts pos­sess two prohibitins, Phb1p and Phb2p, in similarity to mammalian cells. These pro­teins are located in the inner mitochondrial membrane, where they are involved in the processing of newly-synthesized membrane proteins. We demonstrate that the elimination of one or both of the prohibitin genes in yeast markedly diminished the replicative life span of cells that lack fully-functional mitochondria, while having no effect on cells with functioning mitochondria. This deleterious effect was sup­pressed by the deletion of the RAS2 gene. The expression of PHB1 and PHB2 de­clined gradually up to 5-fold during the life span. Cells in which PHB1 was deleted in conjunction with the absence of a mitochondrial genome displayed remarkable changes in mitochondrial morphology, distribution, and inheritance. This loss of mi- tochondrial integrity was not seen in cells devoid of PHB1 but possessing an intact mitochondrial genome. In a subset of the cells, the changes in mitochondrial integ­rity were associated with increased production of reactive oxygen species, which co-localized with the altered mitochondria. The mitochondrial deficits described above were all suppressed by deletion of RAS2. Our data, together with published information, are interpreted to provide a unified view of the role of the prohibitins in yeast aging. This model posits that the key initiating event is a decline in mitochondrial function, which leads to progressive oxidative damage that is exacerbated in the absence of the prohibitins. This aggravation of the initial damage is ameliorated by the suppression of the production of mitochondrial proteins in the absence of Ras2p signaling of mitochondrial biogenesis.

Wydawca

-

Rocznik

Tom

50

Numer

4

Opis fizyczny

p.1039-1056,fig.,ref.

Twórcy

  • Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
autor
autor
autor
autor

Bibliografia

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Bibliografia

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