title: Interactions between mitochondria and the transcription factor myocyte enhancer factor 2 (MEF2) regulate neuronal structural and functional plasticity and metaplasticity.
abstract: The classical view of mitochondria as housekeeping organelles acting in the background to simply maintain cellular energy demands has been challenged by mounting evidence of their direct and active participation in synaptic plasticity in neurons. Time-lapse imaging has revealed that mitochondria are motile in dendrites, with their localization and fusion and fission events regulated by synaptic activity. The positioning of mitochondria directly influences function of nearby synapses through multiple pathways including control over local concentrations of ATP, Ca(2+) and reactive oxygen species. Recent studies have also shown that mitochondrial protein cascades, classically associated with apoptosis, are involved in neural plasticity in healthy cells. These findings link mitochondria to the plasticity- and metaplasticity-associated activity-dependent transcription factor myocyte enhancer factor 2 (MEF2), further repositioning mitochondria as potential command centres for regulation of synaptic plasticity. Intriguingly, MEF2 and mitochondrial functions appear to be intricately intertwined, as MEF2 is a target of mitochondrial apoptotic caspases and, in turn, MEF2 regulates mitochondrial genome transcription essential for production of superoxidase and hydrogen peroxidase. Here, we review evidence supporting mitochondria as central organelles controlling the spatiotemporal expression of neuronal plasticity, and attempt to disentangle the MEF2-mitochondria relationship mediating these functions.
authors.affiliation: Department of Cellular and Physiological Sciences and the Brain Research Centre, University of British Columbia, Vancouver, BC, Canada, V6T2B5.
authors.forename: Janaina
authors.initials: J
authors.lastname: Brusco
authors.affiliation: Department of Cellular and Physiological Sciences and the Brain Research Centre, University of British Columbia, Vancouver, BC, Canada, V6T2B5.
authors.forename: Kurt
authors.initials: K
authors.lastname: Haas
mesh_terms: D000818:Animals; D064326:MEF2 Transcription Factors / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology
chemical_list: D064326:MEF2 Transcription Factors