%0 Journal Article
%T The Phosphorylation-Dependent Regulation of Mitochondrial Proteins in Stress Responses
%A Yusuke Kanamaru
%A Shiori Sekine
%A Hidenori Ichijo
%A Kohsuke Takeda
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/931215
%X To maintain cellular homeostasis, cells are equipped with precise systems that trigger the appropriate stress responses. Mitochondria not only provide cellular energy but also integrate stress response signaling pathways, including those regulating cell death. Several lines of evidence suggest that the mitochondrial proteins that function in this process, such as Bcl-2 family proteins in apoptosis and phosphoglycerate mutase family member 5 (PGAM5) in necroptosis, are regulated by several kinases. It has also been suggested that the phosphorylation-dependent regulation of mitochondrial fission machinery, dynamin-related protein 1 (Drp1), facilitates appropriate cellular stress responses. However, mitochondria themselves are also damaged by various stresses. To avoid the deleterious effects exerted by damaged mitochondria, cells remove these mitochondria in a selective autophagic degradation process called mitophagy. Interestingly, several kinases, such as PTEN-induced putative kinase 1 (PINK1) in mammals and stress-responsive mitogen-activated protein (MAP) kinases in yeast, have recently been shown to be involved in mitophagy. In this paper, we focus on the phosphorylation-dependent regulation of mitochondrial proteins and discuss the roles of this regulation in the mitochondrial and cellular stress responses. 1. Introduction Mitochondria play a fundamental role in cells, serving as the ¡°powerhouses¡± that produce ATP through the process of oxidative phosphorylation. In addition to supplying cellular energy, mitochondria are involved in the response to several cellular stresses, such as cell death signaling and antiviral immunity [1¨C3]. However, mitochondria themselves are also exposed to various stresses. For example, leakage of the high-energy electrons in the respiratory chain leads to the formation of reactive oxygen species (ROS), which can damage mitochondrial DNA (mtDNA). Mutations in mtDNA result in enzymatic abnormalities in the mitochondrial respiratory chain and further oxidative stress. This vicious cycle has been considered to be involved in a wide range of human diseases, such as metabolic, aging, and neurodegenerative diseases [4]. Thus, the quality of mitochondria must be continuously monitored and maintained by various strategies. Mitochondria are dynamic organelles that constantly fuse and divide [5]. These dynamic properties are important for the maintenance of mitochondrial functions, which ultimately contribute to cell survival. A certain degree of mitochondrial damage, including mtDNA mutations, can be rescued by mitochondrial
%U http://www.hindawi.com/journals/jst/2012/931215/