Type

Journal Article

Authors

David C Henshall
Clara K Schindler
Eva M Jimenez-Mateos
Claire M Mooney
Mark Dunleavy
Patrick Chang
Amaya Sanz-Rodriguez
Jaime Martinez-Villarreal
Tobias Engel
Aurelien Caballero-Caballero

Subjects

Biochemistry

Topics
chromatin immunoprecipitation class brain epilepsy temporal lobe localization forkhead transcription factors transcription factor status epilepticus

Mitochondrial localization of the Forkhead box class O transcription factor FOXO3a in brain. (2012)

Abstract FOXO3a is member of the Forkhead box class O transcription factors, which functions in diverse pathways to regulate cellular metabolism, differentiation, and apoptosis. FOXO3a shuttles between the cytoplasm and nucleus and may be activated in neurons by stressors, including seizures. A subset of nuclear transcription factors may localize to mitochondria, but whether FOXO3a is present within brain mitochondria is unknown. Here, we report that purified mitochondrial fractions from rat, mouse, and human hippocampus, as well as HT22 hippocampal cells, contain FOXO3a protein. Immunogold electron microscopy supported the presence of FOXO3a within brain mitochondria, and chromatin immunoprecipitation analysis suggested FOXO3a was associated with mitochondrial DNA. Over-expression of a mitochondrially targeted FOXO3a fusion protein in HT22 cells, but not primary hippocampal neurons, conferred superior protection against glutamate toxicity than FOXO3a alone. Mitochondrial FOXO3a levels were reduced in the damaged region of the mouse hippocampus after status epilepticus, while mitochondrial fractions from the hippocampus of patients with temporal lobe epilepsy displayed higher levels of FOXO3a than controls. These results support mitochondria as a site of FOXO3a localization, which may contribute to the overall physiological and pathophysiological functions of this transcription factor.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Clara K Schindler, Eva M Jimenez-Mateos, Claire M Mooney, Mark Dunleavy, Patrick Chang, Amaya Sanz-Rodriguez, Jaime Martinez-Villarreal, Tobias Engel, Aurelien Caballero-Caballero

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55
 
3
Claire Mooney
Royal College of Surgeons in Ireland
Total Publications: 8
 
4
Amaya Sanz-Rodriguez
Royal College of Surgeons in Ireland
Total Publications: 18
 
5
Jaime Martinez-Villarreal
Royal College of Surgeons in Ireland
Total Publications: 3
 
6
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66