Decreased Cytochrome-c Oxidase Activity and Lack of Age-Related Accumulation of Mitochondrial DNA Deletions in the Brains of Schizophrenics

Cardiac hypertrophy was produced in embryonic chicks by decreasing the incubation temperature from 38 degrees C to 32 degrees C on day 11. Increases in ventricular protein, RNA, and DNA support the cardiac enlargement. Cytochrome-c oxidase activity and citrate synthase activity were depressed in hypothermic ventricles by 63% and 56%, respectively. No significant differences were seen in enzyme activities in pectoralis muscles. The involvement of mitochondrial gene replication and transcription was evaluated using a cDNA clone for the mitochondrially encoded subunit III of cytochrome-c oxidase (CO III). Quantitative slot-blot analysis demonstrated that the relative CO III mRNA concentration was reduced in hypothermic ventricles. In contrast, the relative mitochondrial DNA concentration was increased in hypothermic ventricles. Taken together, these data indicate that a hypothermia-induced decrease in cytochrome-c oxidase activity is associated with a decrease in CO III mRNA, which is not coupled to a decrease in the mitochondrial DNA copy number. This dissociation of mitochondrial gene replication and transcription may provide a useful model for examining the regulation of mitochondrial biogenesis.

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Age-related modifications of cytochrome c oxidase activity in discrete brain regions

Mechanisms of Ageing and Development ◽

10.1016/0047-6374(90)90024-a ◽

1990 ◽

Vol 55 (2) ◽

pp. 171-180 ◽

Cited By ~ 59

Author(s):

D. Curti ◽

M.C. Giangare ◽

M.E. Redolfi ◽

I. Fugaccia ◽

G. Benzi

Keyword(s):

Cytochrome C ◽

Cytochrome C Oxidase ◽

Oxidase Activity ◽

Brain Regions ◽

Age Related

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Mitochondrial DNA deletions and cytochrome c oxidase deficiency in muscle fibres

Journal of the Neurological Sciences ◽

10.1016/0022-510x(92)90025-g ◽

1992 ◽

Vol 110 (1-2) ◽

pp. 169-177 ◽

Cited By ~ 45

Author(s):

Anders Oldfors ◽

Nils-Göran Larsson ◽

Elisabeth Holme ◽

Már Tulinius ◽

Bernhard Kadenbach ◽

...

Keyword(s):

Mitochondrial Dna ◽

Cytochrome C ◽

Cytochrome C Oxidase ◽

Muscle Fibres ◽

Oxidase Deficiency ◽

Cytochrome C Oxidase Deficiency ◽

Dna Deletions

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Oxyphil Cell Metaplasia in the Parathyroids Is Characterized by Somatic Mitochondrial DNA Mutations in NADH Dehydrogenase Genes and Cytochrome c Oxidase Activity–Impairing Genes

American Journal Of Pathology ◽

10.1016/j.ajpath.2014.07.015 ◽

2014 ◽

Vol 184 (11) ◽

pp. 2922-2935 ◽

Cited By ~ 8

Author(s):

Josef Müller-Höcker ◽

Sabine Schäfer ◽

Stefan Krebs ◽

Helmut Blum ◽

Gábor Zsurka ◽

...

Keyword(s):

Mitochondrial Dna ◽

Cytochrome C ◽

Cytochrome C Oxidase ◽

Oxidase Activity ◽

Nadh Dehydrogenase ◽

Mitochondrial Dna Mutations ◽

Dna Mutations ◽

Oxyphil Cell

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Genetic mosaic analysis of a deleterious mitochondrial DNA mutation in Drosophila reveals novel aspects of mitochondrial regulation and function

Molecular Biology of the Cell ◽

10.1091/mbc.e14-11-1513 ◽

2015 ◽

Vol 26 (4) ◽

pp. 674-684 ◽

Cited By ~ 31

Author(s):

Zhe Chen ◽

Yun Qi ◽

Stephanie French ◽

Guofeng Zhang ◽

Raúl Covian Garcia ◽

...

Keyword(s):

Mitochondrial Dna ◽

Cytochrome C ◽

Cytochrome C Oxidase ◽

Mtdna Mutation ◽

Mitochondrial Dna Mutation ◽

Tissue Specific ◽

Dna Mutation ◽

Mtdna Mutations ◽

Genetic Mosaic ◽

Age Related

Various human diseases are associated with mitochondrial DNA (mtDNA) mutations, but heteroplasmy—the coexistence of mutant and wild-type mtDNA—complicates their study. We previously isolated a temperature-lethal mtDNA mutation in Drosophila, mt:CoIT300I, which affects the cytochrome c oxidase subunit I (CoI) locus. In the present study, we found that the decrease in cytochrome c oxidase (COX) activity was ascribable to a temperature-dependent destabilization of cytochrome a heme. Consistently, the viability of homoplasmic flies at 29°C was fully restored by expressing an alternative oxidase, which specifically bypasses the cytochrome chains. Heteroplasmic flies are fully viable and were used to explore the age-related and tissue-specific phenotypes of mt:CoIT300I. The proportion of mt:CoIT300I genome remained constant in somatic tissues along the aging process, suggesting a lack of quality control mechanism to remove defective mitochondria containing a deleterious mtDNA mutation. Using a genetic scheme that expresses a mitochondrially targeted restriction enzyme to induce tissue-specific homoplasmy in heteroplasmic flies, we found that mt:CoIT300I homoplasmy in the eye caused severe neurodegeneration at 29°C. Degeneration was suppressed by improving mitochondrial Ca2+ uptake, suggesting that Ca2+ mishandling contributed to mt:CoIT300I pathogenesis. Our results demonstrate a novel approach for Drosophila mtDNA genetics and its application in modeling mtDNA diseases.

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Induction and characterization of mitochondrial DNA mutants in Chlamydomonas reinhardtii.

The Journal of Cell Biology ◽

10.1083/jcb.108.4.1221 ◽

1989 ◽

Vol 108 (4) ◽

pp. 1221-1226 ◽

Cited By ~ 48

Author(s):

R F Matagne ◽

M R Michel-Wolwertz ◽

C Munaut ◽

C Duyckaerts ◽

F Sluse

Keyword(s):

Mitochondrial Dna ◽

Cytochrome C ◽

Chlamydomonas Reinhardtii ◽

Cytochrome C Oxidase ◽

Oxidase Activity ◽

Wild Type ◽

Apocytochrome B ◽

Cytochrome Pathway ◽

Apocytochrome B Gene

In addition to lethal minute colony mutations which correspond to loss of mitochondrial DNA, acriflavin induces in Chlamydomonas reinhardtii a low percentage of cells that grow in the light but do not divide under heterotrophic conditions. Two such obligate photoautotrophic mutants were shown to lack the cyanide-sensitive cytochrome pathway of the respiration and to have a reduced cytochrome c oxidase activity. In crosses to wild type, the mutations are transmitted almost exclusively from the mating type minus parent. A same pattern of inheritance is seen for the mitochondrial DNA in crosses between the two interfertile species C. reinhardtii and Chlamydomonas smithii. Both mutants have a deletion in the region of the mitochondrial DNA containing the apocytochrome b gene and possibly the unidentified URFx gene.

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Decreased cytochrome c mediates an age-related decline of oxidative phosphorylation in rat kidney mitochondria

Biochemical Journal ◽

10.1042/bj20091373 ◽

2010 ◽

Vol 427 (1) ◽

pp. 105-112 ◽

Cited By ~ 36

Author(s):

John F. O'Toole ◽

Hiral V. Patel ◽

Colin J. Naples ◽

Hisashi Fujioka ◽

Charles L. Hoppel

Keyword(s):

Cytochrome C ◽

Oxidative Phosphorylation ◽

Cytochrome C Oxidase ◽

Oxidase Activity ◽

Mitochondrial Morphology ◽

Voltage Dependent Anion Channel ◽

Microscopic Appearance ◽

Spectrophotometric Methods ◽

Fischer 344 ◽

Age Related

Kidney function declines with advancing age and mitochondria have been implicated. In the present study we have examined the integrated function of mitochondria isolated from kidneys of 6- and 24-month-old Fischer 344 rats. OXPHOS (oxidative phosphorylation) of intact mitochondria and cytochrome c oxidase activity in permeabilized mitochondria were determined with polarographic assays. The activities of the ETC (electron transport chain) complexes and the cytochrome content in solubilized mitochondria were measured using spectrophotometric methods. The respiratory complexes were evaluated with blue native gel electrophoresis. Mitochondrial preparations were evaluated by immunoblotting for cytochrome c, Smac/Diablo and VDAC (voltage-dependent anion channel). Mitochondrial morphology was examined by electron microscopy. OXPHOS of mitochondria isolated from 24-month-old animals was decreased 15–25% with complexes I, II, III and IV, and fatty acid substrates. The electron microscopic appearance of mitochondria, the activity of the ETC complexes and the protein abundance of individual complexes and supercomplexes were unchanged. The content of cytochrome c was decreased by 37% in aged mitochondria, as determined by spectrophotometric methods and confirmed with immunoblotting. Polarographic determination of cytochrome c oxidase activity with endogenous cytochrome c demonstrated a 23% reduction in aged mitochondria, which was corrected with the addition of exogenous cytochrome c. Renal mitochondrial OXPHOS decreased with aging in the Fischer 344 rat. Decreased mitochondrial cytochrome c content is a major factor contributing to the OXPHOS defect of mitochondria isolated from kidneys of elderly animals.

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