The Cytosolic Redox is Coupled to VO₂. A Working Hypothesis

Abstract

In aerobic tissues the match between energy demand (ATPase activity) and energy supply (ATP production) requires close integration of the glycolytic and mitochondrial metabolic controls. Since most ATPase activity occurs in the cytosol this integration must be mediated by cytosolic signals. While there is uncertainty about the mechanism, there is general agreement that recruitment of mitochondrial ATP production is strongly coupled to changes in cytosolic phosphorylation state. Although the role of mitochondrial redox has been identified, cytosolic redox has been left out of models of mitochondrial control. Results from three different kinds of studies suggest that in the cell there is a strong interaction between the mitochondrial and cytosolic redox states and mitochondrial metabolism. These results include studies on: 1) intact tissues such as liver (Berry et al, 1980), heart (Kauppinen et al, 1983) and red skeletal muscle (Connett et al, 1986); 2) reconstituted glycolytic and mitochondrial systems (Jong & Davis, 1983) and 3) metabolic models of heart metabolism that include kinetic submodels of most of the individual enzymes (Kohn, 1983). The objective of this paper is to describe a distributed equilibrium hypothesis that accounts for a cooperative interaction between the glycolytic and oxidative metabolic systems under aerobic conditions.