Respiration and substrate transport rates as well as reactive XXXX species production distinguish mitochondria from brain and liver.

@entity1 @entity2125 @entity26 @entity19
BACKGROUND: Aberrant mitochondrial function, including excessive reactive @entity26 species (ROS) production, has been implicated in the pathogenesis of @entity1 diseases. The use of mitochondrial inhibitors to ascertain the sites in the electron transport chain (ETC) resulting in altered ROS production can be an important tool. However, the response of @entity19 mitochondria to ETC inhibitors has not been thoroughly assessed. Here we set out to characterize the differences in phenotypic response to ETC inhibitors between the more energetically demanding brain mitochondria and less energetically demanding liver mitochondria in commonly utilized C57BL/6J @entity19 . RESULTS: We show that in contrast to brain mitochondria, inhibiting distally within complex I or within complex III does not increase liver mitochondrial ROS production supported by complex I substrates, and liver mitochondrial ROS production supported by complex II substrates occurred primarily independent of membrane potential. Complex I, II, and III enzymatic activities and membrane potential were equivalent between liver and brain and responded to ETC. inhibitors similarly. Brain mitochondria exhibited an approximately two-fold increase in complex I and II supported respiration compared with liver mitochondria while exhibiting similar responses to inhibitors. Elevated @entity2125 transport and heightened complex II-III coupled activity accounted for increased complex I and II supported respiration, respectively in brain mitochondria. CONCLUSIONS: We conclude that important mechanistic differences exist between @entity19 liver and brain mitochondria and that @entity19 mitochondria exhibit phenotypic differences compared with mitochondria from other species.
