Effects of Redox Imbalances on the Mitochondrial Disulfide Proteome

Mitochondria are essential organelles. Besides the production of energy in the form of ATP they are involved in important processes like iron-sulfur cluster biogenesis and apoptosis. To ensure that these processes can work in parallel mitochondria exhibit a complex morphology with four distinct subcompartments. The mitochondrial matrix is surrounded by the inner membrane. A second -outer - membrane separates mitochondria from the cytosol and forms an additional compartment, the intermembrane space (IMS). Interestingly, this spatial separation helps to establish a complex redox environment within mitochondria. For example, the mitochondrial IMS is considerably more oxidizing than the cytosol and the matrix. Recent studies indicate that imbalances in the redox environment result in mitochondrial dysfunctions and consequently diseases. However, on a proteomic level it unclear what leads to these dysfunctions. In this study we investigate proteomic changes under varying redox environments using quantitative mass spectrometry. We thereby focus on the influence of the oxidative import machinery and its main component Mia40. The knowledge about these proteomic changes will in the future form the basis for identifying mitochondrial processes affected by redox imbalances. This might help to develop strategies to modulate the mitochondrial redox environment preventing redox imbalances and diseases.