Jan Riemer: "Oxidative folding and redox regulation in mammalian mitochondria"

Jan Riemer
Abteilung für Zellbiologie, Technische Universität Kaiserslautern

Oxidative folding and redox regulation in mammalian mitochondria

For a long time, the endoplasmic reticulum (ER) was considered to be the only compartment of the eukaryotic cell with a dedicated machinery for the introduction of disulfide bonds. However, it recently became evident that eukaryotic cells harbor another oxidizing compartment, the small lumen between the outer and inner membranes of mitochondria - the intermembrane space (IMS). In mitochondria, protein oxidation can be used to drive protein translocation from the cytosol across the outer membrane. Moreover, redox reactions have been implied in the regulation of many IMS-connected processes like apoptosis, aging and respiration.

The machinery responsible for the oxidation of proteins in the IMS has been well characterized in the model organism yeast. Its main components are the oxidoreductase Mia40 that oxidizes and presumably folds substrates and the sulfhydryloxidase Erv1 that reoxidizes Mia40. From Erv1 electrons are transferred to cytochrome c and the respiratory chain thereby avoiding the release of reactive oxygen species. The so far identified substrates of the Mia40-Erv1 disulfide relay encompass two groups of proteins with simple helix-turn-helix folds. Only recently two substrates with more complicated folds – the copper chaperone of superoxide dismutase 1 and Erv1 itself were identified.

Conversely, we know almost nothing about the mechanisms and physiological impact of mitochondrial disulfide bond formation in mammalian cells. In addition, we do not know whether the substrate spectrum in mammalian cells is broader than in yeast. Here, I will present the characterization of the mammalian mitochondrial disulfide relay system by in vivo and in vitro approaches. I will compare and contrast its features with the respective systems in yeast and the machinery for oxidative folding in the ER of mammalian cells.