Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons

David B. Wang, Takuma Uo, Chizuru Kinoshita, Bryce L. Sopher, Rona J. Lee, Sean P. Murphy, Yoshito Kinoshita, Gwenn A. Garden, Hong-Gang Wang, Richard S. Morrison

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Bax-interacting factor 1 (Bif-1, also known as endophilin B1) is a multifunctional protein involved in the regulation of apoptosis, mitochondrial morphology, and autophagy. Previous studies in non-neuronal cells have shown that Bif-1 is proapoptotic and promotes mitochondrial fragmentation. However, the role of Bif-1 in postmitotic neurons has not been investigated. In contrast to non-neuronal cells, we now report that in neurons Bif-1 promotes viability and mitochondrial elongation. In mouse primary cortical neurons, Bif-1 knockdown exacerbated apoptosis induced by the DNA-damaging agent camptothecin. Neurons from Bif-1-deficient mice contained fragmented mitochondria and Bif-1 knockdown in wild-type neurons also resulted in fragmented mitochondria which were more depolarized, suggesting mitochondrial dysfunction. During ischemic stroke, Bif-1 expression was downregulated in the penumbra of wild-type mice. Consistent with Bif-1 being required for neuronal viability, Bif-1-deficient mice developed larger infarcts and an exaggerated astrogliosis response following ischemic stroke. Together, these data suggest that, in contrast to non-neuronal cells, Bif-1 is essential for the maintenance of mitochondrial morphology and function in neurons, and that loss of Bif-1 renders neurons more susceptible to apoptotic stress. These unique actions may relate to the presence of longer, neuron-specific Bif-1 isoforms, because only these forms of Bif-1 were able to rescue deficiencies caused by Bif-1 suppression. This finding not only demonstrates an unexpected role for Bif-1 in the nervous system but this work also establishes Bif-1 as a potential therapeutic target for the treatment of neurological diseases, especially degenerative disorders characterized by alterations in mitochondrial dynamics.

Original languageEnglish (US)
Pages (from-to)2674-2683
Number of pages10
JournalJournal of Neuroscience
Volume34
Issue number7
DOIs
StatePublished - Feb 14 2014

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Neurons
Mitochondria
Stroke
Mitochondrial Dynamics
Apoptosis
Camptothecin
Autophagy
Nervous System
Protein Isoforms
Down-Regulation
Maintenance
DNA
Proteins
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Wang, D. B., Uo, T., Kinoshita, C., Sopher, B. L., Lee, R. J., Murphy, S. P., ... Morrison, R. S. (2014). Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons. Journal of Neuroscience, 34(7), 2674-2683. https://doi.org/10.1523/JNEUROSCI.4074-13.2014
Wang, David B. ; Uo, Takuma ; Kinoshita, Chizuru ; Sopher, Bryce L. ; Lee, Rona J. ; Murphy, Sean P. ; Kinoshita, Yoshito ; Garden, Gwenn A. ; Wang, Hong-Gang ; Morrison, Richard S. / Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 7. pp. 2674-2683.
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Wang, DB, Uo, T, Kinoshita, C, Sopher, BL, Lee, RJ, Murphy, SP, Kinoshita, Y, Garden, GA, Wang, H-G & Morrison, RS 2014, 'Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons', Journal of Neuroscience, vol. 34, no. 7, pp. 2674-2683. https://doi.org/10.1523/JNEUROSCI.4074-13.2014

Bax interacting factor-1 promotes survival and mitochondrial elongation in neurons. / Wang, David B.; Uo, Takuma; Kinoshita, Chizuru; Sopher, Bryce L.; Lee, Rona J.; Murphy, Sean P.; Kinoshita, Yoshito; Garden, Gwenn A.; Wang, Hong-Gang; Morrison, Richard S.

In: Journal of Neuroscience, Vol. 34, No. 7, 14.02.2014, p. 2674-2683.

Research output: Contribution to journalArticle

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AU - Wang, David B.

AU - Uo, Takuma

AU - Kinoshita, Chizuru

AU - Sopher, Bryce L.

AU - Lee, Rona J.

AU - Murphy, Sean P.

AU - Kinoshita, Yoshito

AU - Garden, Gwenn A.

AU - Wang, Hong-Gang

AU - Morrison, Richard S.

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