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Next Article 
Journal of Neuroscience, Vol 13, 1805-1819, Copyright © 1993 by Society for Neuroscience
Mitochondrial and nuclear gene expression for cytochrome oxidase subunits are disproportionately regulated by functional activity in neurons
RF Hevner and MT Wong-Riley
Department of Cellular Biology and Anatomy, Medical College of Wisconsin, Milwaukee 53226.
Mitochondrial respiratory complexes such as cytochrome oxidase (CO) contain
both mitochondrial- and nuclear-encoded subunits. To determine whether
mitochondrial and nuclear gene expression are regulated proportionately in
neurons, we analyzed CO subunit mRNA and mitochondrial DNA (mtDNA) levels
by in situ hybridization and grain counting in the visual system of normal
and monocular TTX-treated monkeys. We compared the regulation of these
molecules with the regulation of CO activity and CO protein, analyzed by
histochemistry and immunohistochemistry, respectively. In normal animals,
CO activity was in general related more closely to mtDNA and CO subunit I
(COI) (mitochondrial-encoded) mRNA levels than to COIV or COVIII (nuclear-
encoded) mRNA levels. For example, puffs (also known as blobs) of high CO
activity in striate cortex were enriched in mtDNA and COI mRNA, but not
COIV or COVIII mRNA. In 3-7 d TTX-treated animals, proportionate decreases
in CO activity and CO protein were observed in specific visual centers;
these changes were accompanied by disproportionate decreases in COI, COIV,
and COVIII mRNA levels. After 7 d of TTX, COI mRNA fell by 49 +/- 3% (mean
+/- SEM) in LGN neurons, while COIV and COVIII mRNAs fell by only 18 +/- 3%
and 29 +/- 3%, respectively. In comparison, CO activity decreased by 23 +/-
2%, and mtDNA by 26 +/- 4%. Qualitative observations in striate cortex also
indicated that COI mRNA changed more than COIV mRNA, COVIII mRNA, mtDNA, or
CO activity. Our results suggest that the local distribution of CO within
neurons, and acute regulatory changes in CO activity occurring over periods
of days are controlled mainly by regulation of the mitochondrial genes that
encode the catalytic subunits of the enzyme.
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