Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics.

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Pancrazi, Laura 
Di Benedetto, Giulietta 
Colombaioni, Laura 
Della Sala, Grazia 
Testa, Giovanna 

Forkhead box g1 (Foxg1) is a nuclear-cytosolic transcription factor essential for the forebrain development and involved in neurodevelopmental and cancer pathologies. Despite the importance of this protein, little is known about the modalities by which it exerts such a large number of cellular functions. Here we show that a fraction of Foxg1 is localized within the mitochondria in cell lines, primary neuronal or glial cell cultures, and in the mouse cortex. Import of Foxg1 in isolated mitochondria appears to be membrane potential-dependent. Amino acids (aa) 277-302 were identified as critical for mitochondrial localization. Overexpression of full-length Foxg1 enhanced mitochondrial membrane potential (ΔΨm) and promoted mitochondrial fission and mitosis. Conversely, overexpression of the C-term Foxg1 (aa 272-481), which is selectively localized in the mitochondrial matrix, enhanced organelle fusion and promoted the early phase of neuronal differentiation. These findings suggest that the different subcellular localizations of Foxg1 control the machinery that brings about cell differentiation, replication, and bioenergetics, possibly linking mitochondrial functions to embryonic development and pathological conditions.

Rett syndrome, autism, brain cortex, cancer, development, Animals, Cell Differentiation, Cell Line, Energy Metabolism, Forkhead Transcription Factors, Green Fluorescent Proteins, Membrane Potential, Mitochondrial, Mice, Mitochondria, Nerve Tissue Proteins
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Proc Natl Acad Sci U S A
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Proceedings of the National Academy of Sciences