VDAC3 has differing mitochondrial functions in two types of striated muscles

Voltage-dependent anion channel (VDAC) is an abundant mitochondrial outer membrane protein. In mammals, three VDAC isoforms have been characterized. We have previously reported alterations in the function of mitochondria when assessed in situ in different muscle types in VDAC1 deficient mice (Anflous et al., 2001). In the present report we extend the study to VDAC3 deficient muscles and measure the respiratory enzyme activity in both VDAC1 and VDAC3 deficient muscles. While in the heart the absence of VDAC3 causes a decrease in the apparent affinity of in situ mitochondria for ADP, in the gastrocnemius, a mixed glycolytic/oxidative muscle, the affinity of in situ mitochondria for ADP remains unchanged. The absence of VDAC1 causes multiple defects in respiratory complex activities in both types of muscle. However, in VDAC3 deficient mice the defect is restricted to the heart and only to complex IV. These functional alterations correlate with structural aberrations of mitochondria. These results demonstrate that, unlike VDAC1, there is muscle-type specificity for VDAC3 function and therefore in vivo these two isoforms may fulfill different physiologic functions.

Research Highlights
► VDAC3 is involved in the transport of ADP across the mitochondrial outer membrane in the cardiac muscle (oxidative muscle) but not in the gastrocnemius muscle (mixed muscle).
► The absence of VDAC3 is associated with altered ultrastructure of mitochondria in the heart but not in the gastrocnemius.
► While the absence of VDAC1 is associated with multiple respiratory chain defects in the heart and the gastrocnemius, the absence of VDAC3 is associated with only complex IV deficiency that is restricted to the heart.
► Unlike VDAC1, VDAC3 fulfills different functions in two types of striated muscles.