A mechanism for accelerated degradation of intracellular proteins after limited damage by free radicals

Abstract

I propose that limited free radical attack upon proteins, occurring continuously in cells, creates new N‐termini (notably aspartate and glutamate) which render the proteins more susceptible to proteolysis by the ubiquitin conjugation system. I suggest that these reactions are a significant part of the previously described ‘N‐end’ and ‘PEST’ rules, which indicate amino acid termini or sequences which tend to dictate short protein half‐lives. I also argue that the N‐end rule may apply to sequestered intracellular sites, such as mitochondria, these also being sites of radical generation.