Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Pancrazi L,Di Benedetto G,Colombaioni L,Della Sala G,Testa G,Olimpico F,Reyes A,Zeviani M,Pozzan T,Costa Mdoi
10.1073/pnas.1515190112subject
Has Abstractpub_date
2015-11-10 00:00:00pages
13910-5issue
45eissn
0027-8424issn
1091-6490pii
1515190112journal_volume
112pub_type
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