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Mitochondrial localization of the Forkhead box class O transcription factor FOXO 3a in brain
Author(s) -
CaballeroCaballero Aurelien,
Engel Tobias,
MartinezVillarreal Jaime,
SanzRodriguez Amaya,
Chang Patrick,
Dunleavy Mark,
Mooney Claire M.,
JimenezMateos Eva M.,
Schindler Clara K.,
Henshall David C.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12133
Subject(s) - mitochondrion , transcription factor , microbiology and biotechnology , forkhead transcription factors , nrf1 , biology , tfam , mitochondrial biogenesis , biochemistry , gene
FOXO 3a is member of the Forkhead box class O transcription factors, which functions in diverse pathways to regulate cellular metabolism, differentiation, and apoptosis. FOXO 3a 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 FOXO 3a is present within brain mitochondria is unknown. Here, we report that purified mitochondrial fractions from rat, mouse, and human hippocampus, as well as HT 22 hippocampal cells, contain FOXO 3a protein. Immunogold electron microscopy supported the presence of FOXO 3a within brain mitochondria, and chromatin immunoprecipitation analysis suggested FOXO 3a was associated with mitochondrial DNA . Over‐expression of a mitochondrially targeted FOXO 3a fusion protein in HT 22 cells, but not primary hippocampal neurons, conferred superior protection against glutamate toxicity than FOXO 3a alone. Mitochondrial FOXO 3a 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 FOXO 3a than controls. These results support mitochondria as a site of FOXO 3a localization, which may contribute to the overall physiological and pathophysiological functions of this transcription factor.