Thiol-dependent redox regulation in the mitochondrial intermembrane space
Jan Riemer, Cellular Biochemistry, University of Kaiserslautern
SUMMARY - Mitochondria are composed of four subcompartments, the outer and inner
membranes, the matrix and the mitochondrial intermembrane space (IMS). IMS proteins
fulfill a plethora of functions in protein import, folding and degradation, in apoptosis, the
degradation of reactive oxygen species (ROS), the exchange of metabolites and the signaling
from mitochondria to the remainder of the cell.
In addition, the IMS is a key hotspot for redox pathways: It harbors a highly reducing
glutathione pool that is in contact with the cytosol, it is in close proximity to the respiratory
chain, and it contains a number of redox-active enzymes most of them likely at very low
amounts. The interplay of oxidizing and reducing pathways is carefully controlled and
balanced because deviations might influence or impair IMS-localized processes or induce
redox signaling events within mitochondria and to the remainder of the cell.
Importantly, our knowledge on the identity of potential IMS-localized redox regulation events
and their molecular mechanisms is very limited. With the proposed project we would
therefore like to identify targets of redox regulation in the IMS and characterize their
regulation in molecular detail. We will therefore rely on a variety of biochemical and cell
biological methods in yeast and mammalian tissue culture cells as well as utilize purified
proteins and mouse models.
PROJECT-RELATED PUBLICATIONS
1. Fischer M, Horn S, Belkacemi A, Kojer K, Petrungaro C, Habich M, Ali M, Küttner V, Bien M,
Kauff F, Dengjel J, Herrmann JM, Riemer J. Protein import and oxidative folding in the
mitochondrial intermembrane space of intact mammalian cells.
Mol Biol Cell, (2013) 24(14):2160-70.
2. Kojer K, Bien M, Gangel H, Morgan B, Dick TP, Riemer J. Redox dynamics of glutathione in the
mitochondrial intermembrane space impact the Mia40 redox state.
EMBO J, (2012) 31(14):3169-82.
3. Klöppel C, Suzuki S, Kojer K, Petrungaro C, Longen S, Fiedler S, Keller S, Riemer J. Mia40dependent oxidation of cysteines in Domain I of Ccs1 controls its distribution between
mitochondria and the cytosol.
Mol Biol Cell, (2011) 22(20):3749-57.
4. Bien M, Longen S, Mesecke N, Chwalla I, Herrmann JM, Riemer J. Mitochondrial disulfide
oxidation is driven by intersubunit disulfide transfer in Erv1 and proof read by glutathione.
Mol Cell, (2010) 37(4): 516-528.
5. Riemer J, Appenzeller-Herzog C, Johansson L, Bodenmiller B, Hartmann-Petersen R and Ellgaard
L A luminal flavoprotein in endoplasmic reticulum-associated degradation.
Proc Nat Acad Sci, (2009) 106(35): 14831-6.
6. Appenzeller-Herzog C, Riemer J, Christensen B, Soerensen S and Ellgaard L. A novel disulfide
switch mechanism in Ero1α balances ER oxidation in human cells.
EMBO J, (2008) 27(22):2977-87.