Functional disorders of the oxidative phosphorylation system in the heart mitochondria of mice with juvenile visceral steatosis

Mice with juvenile visceral steatosis (JVS) develop remarkable cardiac hypertrophy and exhibit an increased number of mitochondria in their heart. However, the biochemical characteristics and physiological functions of these mitochondria cardiac are little known. Here we show that the respiratory activities at state 3 with glutamate plus malate or succinate in the heart mitochondria of JVS mice were greatly decreased to 47% or 77%, respectively, compared with those of control mice. The contents of cytochromes a+a(3), b, and c+c(1) in the heart mitochondria of these mice were also decreased, to 51%, 45%, and 79%, respectively, of those of the control mice. Oligomycin-sensitive ATPase activitiy in these mitochondria, however, was increased to about 2 times over that of the control mice. Surprisingly, the ATP-Pi exchange activity of the heart mitochondria of JVS mice was greatly decreased, to 35% of that of control mice. On the other hand, the expression levels of 2 subunits of H(+)-ATP synthase, i.e., coupling factor 6 and alpha subunit, in heart mitochondria from control and JVS mice were almost the same. These results indicate that the coordinate regulation of mitochondrial proliferation and gene expression for components of the oxidative phosphorylation system was markedly defective in the heart of JVS mice. Our current results also suggest the presence of a novel regulatory mechanisms of ATP synthase activities in the heart.