Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics

Laura Pancrazi, Giulietta Di Benedetto, Laura Colombaioni, Grazia Della Sala, Giovanna Testa, Francesco Olimpico, Aurelio Reyes, Massimo Zeviani, Tullio Pozzan, Mario Costa

Research output: Contribution to journalArticlepeer-review

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 (δm) 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.

Original languageEnglish
Pages (from-to)13910-13915
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number45
DOIs
Publication statusPublished - Nov 10 2015

ASJC Scopus subject areas

  • General

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