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The production of all blood cells from hematopoietic stem cells (HSC) is highly sensitive to reactive oxygen species (ROS). Cumulating evidence suggests that mitochondria are critical for HSC fate determination. FOXO are known regulators of anti-oxidant response and key to the maintenance of HSC. Recent works indicate that FOXO3 is implicated in the control of mitochondrial function beyond regulating levels of ROS in HSC. Here we review these findings and discuss implications for homeostatic blood formation and stem cell fate determination.

Mitochondria and FOXO3 in stem cell homeostasis, a window into hematopoietic stem cell fate determination