Bigenomic Regulation of Cytochrome c Oxidase in Neurons and the Tight Coupling Between Neuronal Activity and Energy Metabolism

  • Margaret T. T. Wong-RileyEmail author
Part of the Advances in Experimental Medicine and Biology book series (volume 748)


Cytochrome c oxidase is the terminal enzyme of the mitochondrial electron transport chain, without which oxidative metabolism cannot be carried to completion. It is one of only four unique, bigenomic proteins in mammalian cells. The holoenzyme is made up of three mitochondrial-encoded and ten nuclear-encoded subunits in a 1:1 stoichiometry. The ten nuclear subunit genes are located in nine different chromosomes. The coordinated regulation of such a multisubunit, multichromosomal, bigenomic enzyme poses a challenge. It is especially so for neurons, whose mitochondria are widely distributed in extensive dendritic and axonal processes, resulting in the separation of the mitochondrial from the nuclear genome by great distances. Neuronal activity dictates COX activity that reflects protein amount, which, in turn, is regulated at the transcriptional level. All 13 COX transcripts are up- and downregulated by neuronal activity. The ten nuclear COX transcripts and those for Tfam and Tfbms important for mitochondrial COX transcripts are transcribed in the same transcription factory. Bigenomic regulation of all 13 transcripts is mediated by nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2). NRF-1, in addition, also regulates critical neurochemicals of glutamatergic synaptic transmission, thereby ensuring the tight coupling of energy metabolism and neuronal activity at the molecular level in neurons.


NMDA Receptor Neuronal Activity AMPA Receptor Tight Coupling Glutamatergic Neurotransmission 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author expresses her deep appreciation for the valuable contributions from her past and present colleagues in her laboratory as well as in the relevant fields of bioenergetics and neuroscience. She also appreciates the continuous support from the National Institutes of Health. The current support is from NIH grant EY018441.


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Cell Biology, Neurobiology and AnatomyMedical College of WisconsinMilwaukeeUSA

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