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 journalArticle

14 Citations (Scopus)

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

Fingerprint

Energy Metabolism
Cell Differentiation
Mitochondria
Mitochondrial Dynamics
Amino Acids
Mitochondrial Membrane Potential
Prosencephalon
Mitosis
Neuroglia
Organelles
Membrane Potentials
Embryonic Development
Transcription Factors
Cell Culture Techniques
Pathology
Cell Line
Neoplasms
Proteins

ASJC Scopus subject areas

  • General

Cite this

Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics. / Pancrazi, Laura; Benedetto, Giulietta Di; Colombaioni, Laura; Sala, Grazia Della; Testa, Giovanna; Olimpico, Francesco; Reyes, Aurelio; Zeviani, Massimo; Pozzan, Tullio; Costa, Mario.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 45, 10.11.2015, p. 13910-13915.

Research output: Contribution to journalArticle

Pancrazi, L, Benedetto, GD, Colombaioni, L, Sala, GD, Testa, G, Olimpico, F, Reyes, A, Zeviani, M, Pozzan, T & Costa, M 2015, 'Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 45, pp. 13910-13915. https://doi.org/10.1073/pnas.1515190112
Pancrazi, Laura ; Benedetto, Giulietta Di ; Colombaioni, Laura ; Sala, Grazia Della ; Testa, Giovanna ; Olimpico, Francesco ; Reyes, Aurelio ; Zeviani, Massimo ; Pozzan, Tullio ; Costa, Mario. / Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 45. pp. 13910-13915.
@article{398de1f91f7f4970aa36f505a23d6f28,
title = "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 (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.",
author = "Laura Pancrazi and Benedetto, {Giulietta Di} and Laura Colombaioni and Sala, {Grazia Della} and Giovanna Testa and Francesco Olimpico and Aurelio Reyes and Massimo Zeviani and Tullio Pozzan and Mario Costa",
year = "2015",
month = "11",
day = "10",
doi = "10.1073/pnas.1515190112",
language = "English",
volume = "112",
pages = "13910--13915",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "45",

}

TY - JOUR

T1 - Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics

AU - Pancrazi, Laura

AU - Benedetto, Giulietta Di

AU - Colombaioni, Laura

AU - Sala, Grazia Della

AU - Testa, Giovanna

AU - Olimpico, Francesco

AU - Reyes, Aurelio

AU - Zeviani, Massimo

AU - Pozzan, Tullio

AU - Costa, Mario

PY - 2015/11/10

Y1 - 2015/11/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84946771630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946771630&partnerID=8YFLogxK

U2 - 10.1073/pnas.1515190112

DO - 10.1073/pnas.1515190112

M3 - Article

VL - 112

SP - 13910

EP - 13915

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 45

ER -