Mitochondrial fission and fusion in secondary brain damage after CNS insults.
Mitochondria are dynamically active organelles, regulated through fission and fusion events to continuously redistribute them across axons, dendrites, and synapses of neurons to meet bioenergetics requirements and to control various functions, including cell proliferation, calcium buffering, neurotransmission, oxidative stress, and apoptosis. However, following acute or chronic injury to CNS, altered expression and function of proteins that mediate fission and fusion lead to mitochondrial dynamic imbalance. Particularly, if the fission is abnormally increased through pro-fission mediators such as Drp1, mitochondrial function will be impaired and mitochondria will become susceptible to insertion of proapototic proteins. This leads to the formation of mitochondrial transition pore, which eventually triggers apoptosis. Thus, mitochondrial dysfunction is a major promoter of neuronal death and secondary brain damage after an insult. This review discusses the implications of mitochondrial dynamic imbalance in neuronal death after acute and chronic CNS insults.
Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA.
Justin
J
Balog
Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA.|William S. Middleton Veterans Administration Hospital, Madison, WI, USA.
Suresh L
SL
Mehta
Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA vemuganti@neurosurgery.wisc.edu.|Neuroscience Training Program, University of Wisconsin, Madison, WI, USA.|Cellular & Molecular Pathology Training Program, University of Wisconsin, Madison, WI, USA.|William S. Middleton Veterans Administration Hospital, Madison, WI, USA.
Raghu
R
Vemuganti
D001930:Brain Injuries / Q000209:etiology*; D002490:Central Nervous System / Q000293:injuries* / Q000648:ultrastructure; D006801:Humans; D063154:Mitochondrial Dynamics
Apoptosis; fission; fusion; mitochondria; neuroprotection
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