Copper and zinc containing superoxide dismutase (CuZnSOD) is located primarily in the cytosol but a small amount of the enzyme has also been identified in the intermembrane space of mitochondria (termed here IMS CuZnSOD). Using Saccharomyces cerevisiae mutants depleted of either isoform of VDAC (voltage-dependent anion-selective channel), we have shown that the activity of IMS CuZnSOD coincides with the presence of a given VDAC isoform and changes in a growth phase dependent way. Moreover, the IMS CuZnSOD activity correlates with the levels of O-2(.-) release from mitochondria and the cytosol redox state. The latter in turn seems to influence the levels of the mitochondrial outer membrane channel protein other than VDAC. Thus, we conclude that in the case of S. cerevisiae both VDAC isoforms influence the IMS CuZnSOD activity and subsequently the expression levels of some mitochondrial proteins. (c) 2007 Elsevier Inc. All rights reserved.