Cellular Aging and Protein Quality Control

Proteins are the building blocks and functional components of the cell, and maintenance of proper protein function is crucial for cellular viability. The protein quality control system is coordinated to maintain a balance between protein production, folding and degradation. This ensures that the newly synthesized proteins fold into their correct three-dimensional shape, while misfolded proteins are either refolded, degraded or sequestered into spatial quality control compartments. If the balance of protein homeostasis, or proteostasis, is disrupted, then misfolded proteins start to accumulate into large aggregates that can interfere with cellular functions.
As a cell ages, the capacity of the protein quality control system declines and the burden of oxidative stress becomes overwhelming and protein aggregates start to build up in the cell. These protein aggregates function as aging factors and are one of the determinants of cellular lifespan. During cell division, it is crucial that such damaging aging factors are retained within the progenitor cell so that the newly formed progeny is born without any damage. If the newly formed cell is born with a high load of these aging factors, it is aged already at birth and will not live as long as a normal damage-free cell.

We use the unicellular yeast Saccharomyces cerevisiae to study how protein aggregates form in a cell during stress and aging. Using in vivo microscopy methods and genome-wide approaches along with biochemical assays we try to elucidate how protein aggregates are recognized and managed by the protein quality control system. We want to know how protein aggregates are sorted into distinct quality control sites to relieve aggregate toxicity, and how this relates to cellular longevity. We also study the process of damage retention during cell division, and aim at identifying the molecular mechanisms behind this rejuvenation process.