Significance The correct interplay between mitochondria and nuclear functions is essential to generate the mature functional six-layered structure of the mammalian cerebral cortex. Thus, alteration in this interaction results in pathological conditions such as cancer or neurodevelopmental disorders. The molecules and signaling mechanisms responsible for the nucleus–mitochondria communication and functional coordination are still largely unknown. The here-reported nuclear and mitochondrial localization of Forkhead box g1 (Foxg1), a transcription factor essential for brain development and cerebral cortex layering, provides insights on the molecular mechanisms through which Foxg1 acts as a link among mitochondrial function, neuronal differentiation, and pathological conditions.