A role for the actin cytoskeleton in cell death and aging in yeast.
Several determinants of aging, including metabolic capacity and genetic stability, are recognized in both yeast and humans. However, many aspects of the pathways leading to cell death remain to be elucidated. Here we report a role for the actin cytoskeleton both in cell death and in promoting longevity. We have analyzed yeast strains expressing mutants with either increased or decreased actin dynamics. We show that decreased actin dynamics causes depolarization of the mitochondrial membrane and an increase in reactive oxygen species (ROS) production, resulting in cell death. Important, however, is the demonstration that increasing actin dynamics, either by a specific actin allele or by deletion of a gene encoding the actin-bundling protein Scp1p, can increase lifespan by over 65%. Increased longevity appears to be due to these cells producing lower than wild-type levels of ROS. Homology between Scp1p and mammalian SM22/transgelin, which itself has been isolated in senescence screens, suggests a conserved mechanism linking aging to actin stability.
Gourlay
Campbell W
CW
Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
Carpp
Lindsay N
LN
Timpson
Paul
P
Winder
Steven J
SJ
Ayscough
Kathryn R
KR
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000502:physiology; D000935:Antifungal Agents / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D047630:Depsipeptides; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D000199:Actins; D000935:Antifungal Agents; D047630:Depsipeptides; D008840:Microfilament Proteins; D010456:Peptides, Cyclic; D017382:Reactive Oxygen Species; C483531:SCP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C057531:jasplakinolide; D020169:Caspases