Intermembrane space proteome of yeast mitochondria

15.09.2012

Voegtle FN, Burkhart JM, Rao S, Gerbeth C, Hinrichs J, Martinou JC, Chacinska A, Sickmann A, Zahedi RP, Meisinger C.

Mol Cell Proteomics. 2012; 11(12):1840-52

Mol Cell Proteomics            online article

The intermembrane space (IMS) represents the smallest subcompartment of mitochondria. Nevertheless, it plays important roles in transport and modification of proteins, lipids or metal ions and for the regulation and assembly of the respiratory chain complexes. Moreover it is involved in many redox processes and coordinates key steps in programmed cell death. We present here the first proteome of the mitochondrial intermembrane space with 51 proteins in total and a coverage of >90%. We found 20 novel intermembrane space proteins out of which 10 have not been localized to mitochondria before. We confirmed IMS localization for 15 proteins using in organello import, protease accessibility upon osmotic swelling and Bax-release assays. Moreover, we identified two novel mitochondrial proteins, Ymr244c-a (Coa6) and Ybl107c (Mic23) as substrates of the MIA import pathway that have unusual cysteine motifs and found the protein phosphatase Ptc5 as a novel substrate of the inner membrane protease IMP. For Coa6 we discovered a role as a novel assembly factor of the cytochrome c oxidase complex. The IMS proteome will serve as a valuable source for further studies on the role of the IMS in cell life and death.