Seminar details

July 7, 2017, 12:00 pm @ MSI-SLT

Dr Prasad Kasturi - Max Planck Institute for Biochemistry, Martinsried, Germany

Host: Prof Tom Owen-Hughes

Proper functional balance of the cellular proteome is vital for all living cells. Failure of this balance results in disturbance of protein homeostasis (proteostasis). Keeping the proteostasis in proper balance is a challenging task, especially in the face of various external and endogenous stress that accumulate during aging. Thus, cells maintain a sophisticated proteostasis network (PN) to monitor and protect their proteome. During aging, perturbations occur in the PN. Aging has been associated with a progressive decline of proteostasis resulting in accumulation of toxic protein species involved in several age-related diseases. However, the molecular mechanisms underlying these age-related decline in proteostasis capacity is poorly understood and how this process affects proteome composition remains largely unexplored.

We developed a sensor (metastable luciferase) to monitor proteostasis capacity during stress and aging. In C.elegans, this sensor is able to show tissue specific variation in proteostasis capacity. We also identified and quantified age-related proteome changes in C. elegans by quantitative mass spectrometry-based proteomics. Our data set shows that during aging, the proteome of the worms under goes extensive remodeling, reaching a state of proteome imbalance that affects key components of the proteostasis network. Proteome imbalance is accompanied by widespread protein aggregation. Unexpectedly, in a long-lived mutant strain, accumulation of chaperone-enriched aggregates is more pronounced compared to wild-type. This suggests that protein aggregation may occur not just as a consequence of proteostasis decline, but may also be induced to improve proteostasis by sequestering surplus, potentially harmful protein species.