%0 Journal Article
%T Mitochondrial Stress Signaling Promotes Cellular Adaptations
%A Jayne Alexandra Barbour
%A Nigel Turner
%J International Journal of Cell Biology
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/156020
%X Mitochondrial dysfunction has been implicated in the aetiology of many complex diseases, as well as the ageing process. Much of the research on mitochondrial dysfunction has focused on how mitochondrial damage may potentiate pathological phenotypes. The purpose of this review is to draw attention to the less well-studied mechanisms by which the cell adapts to mitochondrial perturbations. This involves communication of stress to the cell and successful induction of quality control responses, which include mitophagy, unfolded protein response, upregulation of antioxidant and DNA repair enzymes, morphological changes, and if all else fails apoptosis. The mitochondrion is an inherently stressful environment and we speculate that dysregulation of stress signaling or an inability to switch on these adaptations during times of mitochondrial stress may underpin mitochondrial dysfunction and hence amount to pathological states over time. 1. Introduction Approximately 1.45 billion years ago, gram negative bacteria were engulfed by primitive eukaryotic cells giving rise to the mitochondrion [1¨C3]. However, the complex relationship between this organelle and its host is not fully understood, and the critical role that mitochondria play in various disease states has only been appreciated in recent years. Nuclear encoded proteins coordinate with mitochondrially encoded proteins for the biogenesis and maintenance of the complete mitoproteome. In return, mitochondria produce 90% of the cells ATP. Despite this elegant symbiosis, the inherent differences between mitochondria and the rest of the cell can lead to complications that may ultimately have pathological consequences. For instance, mtDNA release can stimulate an inflammatory response in the host cell [4]. Mitochondria possess a harsh protein folding environment, due to the high levels of reactive oxygen species (ROS), and the fact that more than 99% of mitochondrial proteins need to be transported from the cytosol into the mitochondria and correctly folded. In addition to proteotoxic stress, mitochondria are highly susceptible to DNA mutations from ROS and a high DNA replication error rate, which is confounded by less sophisticated DNA repair mechanisms [5]. Being the site of programmed cell death and energy metabolism, the cells survival is ultimately dependent on precise coordination between mitochondria and the rest of the cell. Consequently there are a number of mitochondrial stress signals that are communicated to the rest of the cell that stimulate cellular adaptions, which support this organelle-host
%U http://www.hindawi.com/journals/ijcb/2014/156020/