FUNCTIONING OF CYTOCHROME c OXIDASE IN THE MITOCHONDRIAL MEMBRANE AND IN VESICLES

We examined some of the potential mechanisms lungfish ( Protopterus dolloi ) use to regulate cytochrome c oxidase (CCO), during metabolic depression. CCO activity was reduced by 67% in isolated liver mitochondria of estivating fish. This was likely accomplished, in part, by the 46% reduction in CCO subunit I protein expression in the liver. No change in the mRNA expression levels of CCO subunits I, II, III, and IV were found in the liver, suggesting CCO is under translational regulation; however, in the kidney, messenger limitation may be a factor as the expression of subunits I and II were depressed (∼10-fold) during estivation, suggesting tissue-specific mechanisms of regulation. CCO is influenced by mitochondrial membrane phospholipids, particularly cardiolipin (CL). In P. dolloi , the phospholipid composition of the liver mitochondrial membrane changed during estivation, with a ∼2.3-fold reduction in the amount of CL. Significant positive correlations were found between CCO activity and the amount of CL and phosphatidylethanolamine within the mitochondrial membrane. It appears CCO activity is regulated through multiple mechanisms in P. dolloi , and individual subunits of CCO are regulated independently, and in a tissue-specific manner. It is proposed that altering the amount of CL within the mitochondrial membrane may be a means of regulating CCO activity during metabolical depression in the African lungfish, P. dolloi .

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Androgens regulate mitochondrial cytochrome c oxidase and lysosomal hydrolases in mouse skeletal muscle

Biochemical Journal ◽

10.1042/bj1920349 ◽

1980 ◽

Vol 192 (1) ◽

pp. 349-353 ◽

Cited By ~ 27

Author(s):

H Koenig ◽

A Goldstone ◽

C Y Lu

Keyword(s):

Skeletal Muscle ◽

Cytochrome C ◽

Monoamine Oxidase ◽

Cytochrome C Oxidase ◽

Mitochondrial Membrane ◽

Inner Mitochondrial Membrane ◽

Lysosomal Hydrolases ◽

Mouse Skeletal Muscle ◽

Membrane Enzyme ◽

Specific Activities

The gastrocnemius, a fast-twitch white muscle, and the soleus, a slow-twitch red muscle, were studied in A/J mice. The specific activities of the lysosomal hydrolases, beta-D-glucuronidase, hexosaminidase, beta-D-galactosidase and arylsulphatase, the inner-mitochondrial-membrane enzyme cytochrome c oxidase, and the outer-mitochondrial-membrane enzyme monoamine oxidase, were greater in the soleus than in the gastrocnemius. The specific activities of the lysosomal hydrolases and cytochrome c oxidase in the gastrocnemius and soleus were substantially higher in male mice than in female mice. Orchiectomy abolished this sex difference. Testosterone increased the activities of the lysosomal hydrolases and cytochrome c oxidase and coincidentally induced muscle hypertrophy and an accretion of protein and RNA, but total DNA remained constant. Monoamine oxidase was unaffected by sex, orchiectomy and testosterone. These findings indicate that endogenous androgens regulate the activity of enzymes associated with lysosomes and the inner mitochondrial membrane, as well as muscle fibre growth in mouse skeletal muscle.

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Mitochondrial membrane biogenesis: identification of a precursor to yeast cytochrome c oxidase subunit II, an integral polypeptide.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.77.1.142 ◽

1980 ◽

Vol 77 (1) ◽

pp. 142-146 ◽

Cited By ~ 51

Author(s):

K. A. Sevarino ◽

R. O. Poyton

Keyword(s):

Cytochrome C ◽

Cytochrome C Oxidase ◽

Mitochondrial Membrane ◽

Membrane Biogenesis ◽

Oxidase Subunit

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Mitochondrial cytochrome c oxidase: catalysis, coupling and controversies

Biochemical Society Transactions ◽

10.1042/bst20160139 ◽

2017 ◽

Vol 45 (3) ◽

pp. 813-829 ◽

Cited By ~ 38

Author(s):

Peter R. Rich

Keyword(s):

Cytochrome C ◽

Cytochrome C Oxidase ◽

Mitochondrial Membrane ◽

Mitochondrial Cytochrome ◽

Inner Mitochondrial Membrane ◽

Reaction Cycle ◽

Chemical Structures ◽

Catalytic Intermediates ◽

Underlying Mechanisms ◽

Mitochondrial Cytochrome C

Mitochondrial cytochrome c oxidase is a member of a diverse superfamily of haem–copper oxidases. Its mechanism of oxygen reduction is reviewed in terms of the cycle of catalytic intermediates and their likely chemical structures. This reaction cycle is coupled to the translocation of protons across the inner mitochondrial membrane in which it is located. The likely mechanism by which this occurs, derived in significant part from studies of bacterial homologues, is presented. These mechanisms of catalysis and coupling, together with current alternative proposals of underlying mechanisms, are critically reviewed.

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Defective kinetics of cytochrome c oxidase and alteration of mitochondrial membrane potential in fibroblasts and cytoplasmic hybrid cells with the mutation for myoclonus epilepsy with ragged-red fibres (‘MERRF’) at position 8344 nt

Biochemical Journal ◽

10.1042/bj3420537 ◽

1999 ◽

Vol 342 (3) ◽

pp. 537-544 ◽

Cited By ~ 11

Author(s):

Hana ANTONICKÁ ◽

Daniel FLORYK ◽

Petr KLEMENT ◽

Leona STRATILOVÁ ◽

Jana HEŘMANSKÁ ◽

...

Keyword(s):

Membrane Potential ◽

Cytochrome C ◽

Cytochrome C Oxidase ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Control Analysis ◽

Hybrid Cells ◽

Myoclonus Epilepsy ◽

Increased Sensitivity ◽

Hybrid Clones

We have investigated pathogenic effects of the tRNALys A8344G mutation associated with the syndrome myoclonus epilepsy with ragged-red fibres (MERRF) by using fibroblasts and fibroblast-derived cytoplasmic hybrid cells harbouring different percentages of mutated mitochondrial DNA (mtDNA). The activity of cytochrome c oxidase (COX) in patient fibroblasts with 89% mutated mtDNA was decreased to 20% of the control levels. COX exhibited altered kinetics, with a decreased Vmax for both the low-affinity and high-affinity phases; however, the Km values were not significantly changed. The substrate-dependent synthesis of ATP was decreased to 50% of the control. Analysis of the mitochondrial membrane potential, δΨ, in digitonin-treated cells with tetramethylrhodamine methyl ester (TMRM) with the use of flow cytometry showed a 80% decrease in δΨ at state 4 and an increased sensitivity of δΨ to an uncoupler in fibroblasts from the patient. The investigation of transmitochondrial cytoplasmic hybrid clones derived from the patient's fibroblasts enabled us to characterize the relationship between heteroplasmy of the MERRF mutation, COX activity and δΨ. Within the range of 87-73% mutated mtDNA, COX activity was decreased to 5-35% and δΨ was decreased to 6-78%. These results demonstrate that the MERRF mutation affects COX activity and δΨ in different proportions with regard to mutation heteroplasmy and indicate that the biochemical manifestation of the MERRF mutation exerts a very steep threshold of δΨ inhibition.

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The influence of chronic ethanol feeding to rats on liver mitochondrial membrane structure and function

Canadian Journal of Biochemistry ◽

10.1139/o80-154 ◽

1980 ◽

Vol 58 (10) ◽

pp. 1147-1155 ◽

Cited By ~ 26

Author(s):

E. A. Hosein ◽

Hung Lee ◽

Ilan Hofmann

Keyword(s):

Cytochrome C ◽

Cytochrome C Oxidase ◽

Rat Liver ◽

Mitochondrial Membrane ◽

Membrane Structure ◽

Membrane Lipids ◽

Specific Activity ◽

Structure And Function ◽

Membrane Structure And Function ◽

And Function

Arrhenius plots were generated on the activity of rat liver mitochondrial cytochrome c oxidase from Metrecal–sucrose fed controls and Metrecal–alcohol fed experimentals. Chronic alcohol feeding resulted in diminished specific activity of cytochrome c oxidase and abolition of the discontinuity temperature at 17.5 °C found in the controls. Twenty-four hours after alcohol withdrawal, a discontinuity temperature reappeared at 14.4 °C; at 48 h it increased to 22.6 °C and returned to normal (17.4 °C) at 72 h. Such liver mitochondria also showed a decreased capacity to oxidize the acetyl group of acetyl carnitine immediately following prolonged alcohol feeding. When the assay was performed following withdrawal from alcohol 24 h later, oxidation was enhanced and this effect persisted for another 48 h. These latter results revealed a diminished capacity of such mitochondria to oxidize short chain fatty acids during alcohol feeding and the reverse during alcohol withdrawal.These results, complemented by thermographic data obtained through differential scanning calorimetry (DSC) reinforced the view that chronic alcoholic feeding induced adaptive changes in the fluidity of rat liver mitochondrial membrane lipids. Moreover, they demonstrated that in the microenvironment of the membrane-bound enzymes on withdrawal from ethanol, the membrane readapts to the new conditions without alcohol. This involved modulation of membrane structure and function and at the same time demonstrated a role for the membrane in the expression of tolerance and functional dependence on alcohol.

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