The Mitochondrial Disulfide Relay System: Roles in Oxidative Protein Folding and Beyond

Figure 4

Functions of Erv1/ALR. Oxidative Import. Erv1/ALR reoxidizes Mia40. Fe/S Biogenesis. In yeast Erv1/ALR is required for the biogenesis of cytosolic Fe/S proteins but not for mitochondrial Fe/S proteins. Development. Erv1/ALR is expressed during development. Knockdown or chemical inhibition of Erv1/ALR leads to impaired development of organs such as liver and hamper cardiac outgrowth. Mitochondrial Morphology. Erv1/ALR is important for mitochondrial morphology in undifferentiated cells. Knockdown of Erv1/ALR in mouse embryonic stem cells leads to mitochondrial fragmentation and increased levels of Drp1 (dynamin-related protein 1). Hepatic Growth Factor. Extracellular Erv1/ALR increases regenerative capacities of liver tissue. Extracellular Erv1/ALR can bind to a so far unknown receptor. Upon binding tyrosine-phosphorylation of the epidermal growth factor receptor (EGFR) is enhanced which promotes phosphorylation and activation of mitogen activated protein kinase (MAPK). Gene Regulation. A truncated cytosolic form of Erv1/ALR can bind to Jun activating binding protein 1 (JAB1). Binding to JAB1 increases JAB1-mediated phosphorylation of c-Jun. Upon phosphorylation c-Jun can form a complex with AP-1 complex (activator protein 1). In hematopoietic stem cells (HSC) sequestering of JAB1 by ALR prevents binding of JAB1 to p27(kip).