The group set out to see if protein carbonylation, an irreversible form of oxidative damage, increased with age in budding yeast. It did, which immediately led to another question. “How,” asks Nyström, “do the daughters come out fresh”?
The daughters do, indeed, emerge with 3.6-fold less damage than their parents, and if the oxidative load is first boosted in the mother the ratio ratchets up to sixfold. This uneven segregation is dependent on the presence of Sir2p. This protein is required to prevent premature yeast aging, and was thought to operate in yeast solely by reducing the accumulation of toxic circles of rDNA.
The mechanism of oxidative filtering remains unclear. It is dependent on actin, which suggests two possible scenarios. The actin may block nearly all mother proteins from entering the bud, so that the bud is built almost entirely from new protein synthesis. Or carbonylated proteins may be selectively retained in the mother by proteins that use actin as a scaffold. Nyström is testing these possibilities and investigating whether mammalian stem cells might selectively off-load oxidized proteins into their differentiated progeny. ▪