Mitochondrial and nuclear gene expression for cytochrome oxidase subunits are disproportionately regulated by functional activity in neurons. 1993

R F Hevner, and M T 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.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D003576 Electron Transport Complex IV A multisubunit enzyme complex containing CYTOCHROME A GROUP; CYTOCHROME A3; two copper atoms; and 13 different protein subunits. It is the terminal oxidase complex of the RESPIRATORY CHAIN and collects electrons that are transferred from the reduced CYTOCHROME C GROUP and donates them to molecular OXYGEN, which is then reduced to water. The redox reaction is simultaneously coupled to the transport of PROTONS across the inner mitochondrial membrane. Cytochrome Oxidase,Cytochrome aa3,Cytochrome-c Oxidase,Cytochrome Oxidase Subunit III,Cytochrome a,a3,Cytochrome c Oxidase Subunit VIa,Cytochrome-c Oxidase (Complex IV),Cytochrome-c Oxidase Subunit III,Cytochrome-c Oxidase Subunit IV,Ferrocytochrome c Oxygen Oxidoreductase,Heme aa3 Cytochrome Oxidase,Pre-CTOX p25,Signal Peptide p25-Subunit IV Cytochrome Oxidase,Subunit III, Cytochrome Oxidase,p25 Presequence Peptide-Cytochrome Oxidase,Cytochrome c Oxidase,Cytochrome c Oxidase Subunit III,Cytochrome c Oxidase Subunit IV,Oxidase, Cytochrome,Oxidase, Cytochrome-c,Signal Peptide p25 Subunit IV Cytochrome Oxidase,p25 Presequence Peptide Cytochrome Oxidase
D005829 Geniculate Bodies Part of the DIENCEPHALON inferior to the caudal end of the dorsal THALAMUS. Includes the lateral geniculate body which relays visual impulses from the OPTIC TRACT to the calcarine cortex, and the medial geniculate body which relays auditory impulses from the lateral lemniscus to the AUDITORY CORTEX. Lateral Geniculate Body,Medial Geniculate Body,Metathalamus,Corpus Geniculatum Mediale,Geniculate Nucleus,Lateral Geniculate Nucleus,Medial Geniculate Complex,Medial Geniculate Nucleus,Nucleus Geniculatus Lateralis Dorsalis,Nucleus Geniculatus Lateralis Pars Dorsalis,Bodies, Geniculate,Complex, Medial Geniculate,Complices, Medial Geniculate,Corpus Geniculatum Mediales,Geniculate Bodies, Lateral,Geniculate Bodies, Medial,Geniculate Body,Geniculate Body, Lateral,Geniculate Body, Medial,Geniculate Complex, Medial,Geniculate Complices, Medial,Geniculate Nucleus, Lateral,Geniculate Nucleus, Medial,Geniculatum Mediale, Corpus,Geniculatum Mediales, Corpus,Lateral Geniculate Bodies,Medial Geniculate Bodies,Medial Geniculate Complices,Mediale, Corpus Geniculatum,Mediales, Corpus Geniculatum,Nucleus, Geniculate,Nucleus, Lateral Geniculate,Nucleus, Medial Geniculate
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001330 Electronic Data Processing Applications that store and process large quantities of data. Automatic Data Processing,Bar Codes,Computer Data Processing,Data Processing, Automatic,Information Processing, Automatic,Optical Readers,Information Processing,Automatic Information Processing,Bar Code,Codes, Bar,Data Processing, Computer,Data Processing, Electronic,Optical Reader,Processing, Automatic Data,Processing, Automatic Information,Processing, Computer Data,Processing, Electronic Data,Processing, Information
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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