[Role of the p66Shc protein in physiological state and in pathologies]

Abstract

The p66Shc adaptor protein has been in the spotlight of many researchgroups around the world for over adecade. Experiments conducted inrecent years unraveled its structure and enabled the recognition of basic cellular functions. Despite an undoubtedly tremendous progress in the characterization of p66Shc, mechanisms through which this protein potentially impacts the metabolism of mitochondria, and thus the cellular energetics are still waiting to be elucidated. Particularly interesting and profoundly studied is the concept that p66Shc may be a key component of the cell response to oxidative stress which may effectively contribute to the lifespan of the organism. p66Shc phosphorylation at serine 36 triggers a cascade of events leading to an increase in reactive oxygen species (ROS) production. The widely accepted free radical theory of ageing, proposed by Harman inthe - 1950s, assumes that an uncontrolled increase of ROS may lead to oxidation of fundamental cellular components such as proteins and phospholipids even sometimes premature dand cause DNA damage. Accumulation of such lesions in cells may unfavorably affect the functions of tissues and organs, leading to pathologies oreath of the organism. Although well experimentally established, knowledge regarding the involvement of the p66Shc protein in the production of ROS and its impact on the lifespan of organisms remains insufficient and requires a lot of additional research. Further investigation will permit a better understanding ofthe mechanisms governing the processes o f aging andthe emergence of variouspathologies associated with oxidative stress. This work is an attempt to systematize the existing knowledge about the p66Shc protein structure and functions. Another objective was to draw attention to the most interesting aspects and results of in vivo and in vitro studies in different models in the context of oxidative stress-associated pathologies and in aging.