Misfolded Proteins: Maybe not so bad

Author: Hriday Bhambhvani

Institution:  University of Alabama at Birmingham


The mystery of aging has plagued scientists for centuries. Indeed, biologist August Weismann proposed the cell damage theory in 1882 –  “Like components of an aging car, parts of the body eventually wear out from repeated use, killing them and then the body.” The prevailing view of aging today is along the same lines; we age due to increasing cellular malfunction over the years. In general, it is thought that the quality control mechanisms within the cell break down in the aging process. These quality control functions serve to eliminate proteins that are not functional and have lost their typical structure. When quality control functions go awry, misfolded proteins aggregate and contribute to the pathogenesis of a variety of debilitating diseases: Alzheimer’s and Parkinson’s, for example.

However, Dr. Yves Barral, Professor of Biochemistry at ETH Zurich, is of the opinion that this point of view regarding the aging process is limiting. Dr. Barral’s opinion on the subject is informed by a study his group recently published in the journal eLife. Using yeast cells, the group discovered a new type of protein aggregate that forms as cells age. Dr. Barral and his team were able to show that these aggregates do not arise as a result of an impaired internal quality control system. On the contrary, yeast cells that had these protein aggregates displayed better quality control mechanisms. Furthermore, these yeast cells displayed typical protein homeostasis and proteotoxic stress response – the response to misfolded proteins.

The researchers are, as of now, largely unaware of what proteins compose the aggregates, though they have identified one prion-like protein – Sup35 – that is a component. According to Dr. Juha Saarikangas, postdoctoral researcher and first author of the study, “It certainly seems that these aggregates help yeast cells to cope with the physiological changes caused by ageing. We are very excited to learn what type of information is stored in these structures.”

The overarching view held by Professor Barral, his team, and a select group of researchers around the globe is that protein aggregates are not indications of malfunction. Essentially, these aggregations are neither good nor bad according to Barral: “We’re still a fairly small group of scientists who say: aggregate proteins are not pathological – they are neither an accident nor a defect.” Barral and his team do not have an alternate theory of aging, but their results suggest that perhaps pointing the finger at protein aggregation is misguided.