The Phosphorylation-Dependent Regulation of Mitochondrial Proteins in Stress Responses

Yusuke Kanamaru,Hidenori Ichijo,Kohsuke Takeda,Shiori Sekine

doi:10.1155/2012/931215

Abstract

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.

Highlights

Mitochondria play a fundamental role in cells, serving as the “powerhouses” that produce ATP through the process of oxidative phosphorylation
Hog1 and Pbs2 are activated in response to hyperosmotic stress and are involved in the osmoregulatory signal transduction cascade, they are activated under mitophagy-inducing conditions [33]. These findings suggest that mitophagy in yeast is strictly regulated through Atg32 phosphorylation, which is exerted by the interplay of cytosolic stress-responsive mitogen-activated protein (MAP) kinases and the mitochondrial Atg32
Together with the previous report that phosphoglycerate mutase family member 5 (PGAM5) is localized in mitochondria through its N-terminal transmembrane domain [71], these findings indicate that PGAM5 is a novel mitochondriaresident Ser/Thr protein phosphatase that might be involved in the mitochondrial and/or cellular stress responses [69]

Summary

Introduction

Mitochondria play a fundamental role in cells, serving as the “powerhouses” that produce ATP through the process of oxidative phosphorylation. 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]. Mitochondria are dynamic organelles that constantly fuse and divide [5] These dynamic properties are important for the maintenance of mitochondrial functions, which contribute to cell survival. It has been suggested that the phosphorylation-dependent regulation of mitochondrial proteins appear to have important roles in mitochondrial and cellular stress responses. We will summarize recent research related to mitochondria, especially focusing on the phosphorylation-dependent regulation of various mitochondrial proteins

Mitochondria Are Dynamic Organelles

Mitochondria Are Platforms for Apoptosis Execution

Conclusions