Sci. Aging Knowl. Environ., 5 March 2003
Yeast moms bear brunt of protein damage
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/sageke;2003/9/nw35
Key Words: immunocytochemistry elutriation histone deacetylase
Like a mother who'd leap in front of a car to save her child, yeast moms make sacrifices for their offspring. When yeast cells split, the mother hoards tarnished proteins, relieving her daughter of the toxic burden, new research reveals. The study also implicates a longevity-promoting gene in the asymmetric dispersal process, but the details of how cells divvy up damaged proteins remain a mystery.
The yeast Saccharomyces cerevisiae divides unequally, separating into a smaller "daughter" cell and a larger "mother" cell. Each mom generates about 20 offspring before perishing, and every daughter begets her own batch of progeny. Daughters have a normal life span even when they come from older moms, but scientists don't understand how the offspring emerge young. Reactive oxygen species (ROS) disfigure proteins and accumulate over time in many organisms (see "The Two Faces of Oxygen"), so Aguilaniu and colleagues investigated whether yeast cells also amass such injuries.
With age, the yeast collected progressively more proteins that carry carbonyl groups, scars from oxidation. Wondering how daughter cells avoid accumulating such flaws, the investigators used fluorescent antibodies to mark carbonylated proteins, allowing them to spot such proteins in cells at various times during division. After cells pulled apart, daughters glowed only 30% as brightly as the mothers did, indicating that they had one-third as much damage. Then the team doubled the amount of carbonylated proteins in cells by adding the chemical paraquat. After the treated cells divided, mothers carried an even higher percentage of the blemished proteins, suggesting that they took up the excess slag. Using a second fluorescent compound that binds to a particular type of ROS, the researchers showed that mothers and daughters churned out similar amounts of the toxic compound. This observation suggests that the disparity in the amount of carbonyl-marred protein resulted from lopsided allotment of existing proteins rather than a difference in how quickly the cells suffered new damage.
Additional experiments revealed that a gene that influences yeast life span helps control protein distribution when cells split. Yeast live longer when they make extra Sir2 protein and expire young when they lack it (see Kaeberlein Perspective). Aguilaniu and colleagues found that cells without Sir2p parceled carbonylated proteins equally between mother and daughter cells, indicating that unbalanced sorting requires Sir2p.
The study "says that Sir2 is doing even more than we thought," says molecular geneticist Leonard Guarente of the Massachusetts Institute of Technology in Cambridge. The distribution of pocked proteins probably doesn't influence yeast life span, he says, because oxidative stress doesn't limit the number of times yeast can divide. But the sequestration of altered molecules might heighten the fitness of daughter cells by--for instance--keeping growth rates high, he speculates. Geneticist Valter Longo of the University of Southern California in Los Angeles agrees: "There's got to be a system that makes sure that the [daughter], which is going to go out there and represent the population, is as fit as possible." Further studies pinpointing the mechanism by which mothers corral spoiled proteins will reveal how yeast moms throw themselves in harm's way.
--R. John Davenport
March 5, 2003
Science of Aging Knowledge Environment. ISSN 1539-6150