Alternative oxidase causes cell-type- and tissue-specific responses in mutator mice
Here, we set out to test in mtDNA mutator mice how ubiquitous expression of the Ciona intestinalis alternative oxidase (AOX), which attenuates ROS production, affects murine stem-cell pools. We found that AOX does not affect neural stem cells but delays the progression of mutator-driven anemia. Furthermore, when combined with the mutator, AOX potentiates mitochondrial stress and inflammatory responses in skeletal muscle. These differential cell-type-specific findings demonstrate that AOX expression is not a global panacea for curing mitochondrial dysfunction. ROS attenuation must be carefully studied regarding specific underlying defects before AOX can be safely used in therapy.