Mitochondria are key organelles for the maintenance of life and death of the cell, and their morphology is controlled by continual and balanced fission and fusion dynamics. A balance between these events is mandatory for normal mitochondrial and neuronal function, and emerging evidence indicates that mitochondria undergo extensive fission at an early stage during programmed cell death in several neurodegenerative diseases. A pathway for selective degradation of damaged mitochondria by autophagy, known as mitophagy, has been described, and is of particular importance to sustain neuronal viability. In the present work, we analyzed the effect of autophagy stimulation on mitochondrial function and dynamics in a model of remote degeneration after focal cerebellar lesion. We provided evidence that lesion of a cerebellar hemisphere causes mitochondria depolarization in axotomized precerebellar neurons associated with PTEN-induced putative kinase 1 accumulation and Parkin translocation to mitochondria, block of mitochondrial fusion by Mfn1 degradation, increase of calcineurin activity and dynamin-related protein 1 translocation to mitochondria, and consequent mitochondrial fission. Here we suggest that the observed neuroprotective effect of rapamycin is the result of a dual role: (1) stimulation of autophagy leading to damaged mitochondria removal and (2) enhancement of mitochondria fission to allow their elimination by mitophagy. The involvement of mitochondrial dynamics and mitophagy in brain injury, especially in the context of remote degeneration after acute focal brain damage, has not yet been investigated, and these findings may offer new target for therapeutic intervention to improve functional outcomes following acute brain damage.

Cavallucci, V., Bisicchia, E., Cencioni, M., Ferri, A., Latini, L., Nobili, A., Biamonte, F., Nazio, F., Fanelli, F., Moreno, S., Molinari, M., Viscomi, M., D'amelio, M., Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons, <<CELL DEATH & DISEASE>>, N/A; 5 (N/A): e1545-e1545. [doi:10.1038/cddis.2014.511] [http://hdl.handle.net/10807/61701]

Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons

Biamonte, Filippo;Viscomi, Mt;
2014

Abstract

Mitochondria are key organelles for the maintenance of life and death of the cell, and their morphology is controlled by continual and balanced fission and fusion dynamics. A balance between these events is mandatory for normal mitochondrial and neuronal function, and emerging evidence indicates that mitochondria undergo extensive fission at an early stage during programmed cell death in several neurodegenerative diseases. A pathway for selective degradation of damaged mitochondria by autophagy, known as mitophagy, has been described, and is of particular importance to sustain neuronal viability. In the present work, we analyzed the effect of autophagy stimulation on mitochondrial function and dynamics in a model of remote degeneration after focal cerebellar lesion. We provided evidence that lesion of a cerebellar hemisphere causes mitochondria depolarization in axotomized precerebellar neurons associated with PTEN-induced putative kinase 1 accumulation and Parkin translocation to mitochondria, block of mitochondrial fusion by Mfn1 degradation, increase of calcineurin activity and dynamin-related protein 1 translocation to mitochondria, and consequent mitochondrial fission. Here we suggest that the observed neuroprotective effect of rapamycin is the result of a dual role: (1) stimulation of autophagy leading to damaged mitochondria removal and (2) enhancement of mitochondria fission to allow their elimination by mitophagy. The involvement of mitochondrial dynamics and mitophagy in brain injury, especially in the context of remote degeneration after acute focal brain damage, has not yet been investigated, and these findings may offer new target for therapeutic intervention to improve functional outcomes following acute brain damage.
Inglese
Cavallucci, V., Bisicchia, E., Cencioni, M., Ferri, A., Latini, L., Nobili, A., Biamonte, F., Nazio, F., Fanelli, F., Moreno, S., Molinari, M., Viscomi, M., D'amelio, M., Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons, <<CELL DEATH & DISEASE>>, N/A; 5 (N/A): e1545-e1545. [doi:10.1038/cddis.2014.511] [http://hdl.handle.net/10807/61701]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/61701
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