Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics.

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.

authors

Pancrazi L,Di Benedetto G,Colombaioni L,Della Sala G,Testa G,Olimpico F,Reyes A,Zeviani M,Pozzan T,Costa M

doi

10.1073/pnas.1515190112

subject

Has Abstract

pub_date

2015-11-10 00:00:00

pages

13910-5

issue

45

eissn

0027-8424

issn

1091-6490

pii

1515190112

journal_volume

112

pub_type

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