Proteasomes and oxidative stress

Mechanism that Expels Damaged Proteins “Takes a Break” Under Stress

Proteasomes temporarily stop working until oxidative stress dissipates

Researchers at the Technion-Israel Institute of Technology have discovered that the proteasome – the “biological machine” found in each and every one of the body’s cells (and the mechanism by which the body disposes of damaged proteins) – “takes a break” when cells are under harmful oxidative stress. The findings are published this week in Cell Reports.

The team led by Prof. Michael Glickman, of the Technion Faculty of Biology compares the phenomenon to a person caught in a sandstorm closing their eyes until the storm passes to avoid damage.  They found that even after severe damage (which normally can kill cells), proteasomes get back to work properly, as long as the damage is temporary.

Potential damage to cells comes from a long list of sources, including harmful oxidation that can arise as a side effect of the body’s natural energy production.  Such free radicals (reactive oxidative species) attack the body – including the proteins that make up a large portion of human solid body mass.  Resulting damaged proteins must be disposed of quickly, or they will accumulate and cause long-term damage.

Proteasomes remove damaged proteins by recycling them into new proteins. The paradox is that proteasomes themselves are made up of proteins, something that led the researchers to ask: how do proteasomes avoid oxidative stress damage?glikman

“In our experiments, the proteasomes stop working for up to 3 hours during times of stress, with very minor deleterious outcome,” said Prof. Glickman. “In this way, by shielding the protein-recycling mechanism, it reduces potential self-damage during an episode of oxidative stress, and in turn, protects the body from cumulative or unpredictable damage. After such a break, there is a good chance that oxidative stress has passed on, at which time the proteasome can get back to cleaning up the mess left behind.”

The research was conducted as part of Nurit Livnat-Levanon’s doctoral thesis, in collaboration with Noa Reis, microbiologist and lab manager together with Prof Thorsten Hoppe their partner on a Deutsch-Israelische Projektkooperation (DIP) grant at the University of Cologne, Germany.

In the photo: Prof. Michael Glickman. Photographed by: The Technion’s Spokesperson’s Office