Re: mito

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--CABC1 gene mutations cause ubiquinone deficiency with cerebellar

ataxia and seizures.Mollet J, Delahodde A, Serre V, Chretien D,

Schlemmer D, Lombes A, Boddaert N, Desguerre I, de Lonlay P, de

Baulny HO, Munnich A, Rötig A.

INSERM U781 and Department of Genetics, Hôpital Necker-Enfants

Malades, Université René Descartes Paris V, 149 rue de Sèvres, 75015

Paris, France.

Coenzyme Q(10) (CoQ(10)) plays a pivotal role in oxidative

phosphorylation (OXPHOS) in that it distributes electrons between the

various dehydrogenases and the cytochrome segments of the respiratory

chain. Primary coenzyme Q(10) deficiency represents a clinically

heterogeneous condition suggestive of genetic heterogeneity, and

several disease genes have been previously identified. The CABC1

gene, also called COQ8 or ADCK3, is the human homolog of the yeast

ABC1/COQ8 gene, one of the numerous genes involved in the ubiquinone

biosynthesis pathway. The exact function of the Abc1/Coq8 protein is

as yet unknown, but this protein is classified as a putative protein

kinase. We report here CABC1 gene mutations in four ubiquinone-

deficient patients in three distinct families. These patients

presented a similar progressive neurological disorder with cerebellar

atrophy and seizures. In all cases, enzymological studies pointed to

ubiquinone deficiency. CoQ(10) deficiency was confirmed by decreased

content of ubiquinone in muscle. Various missense mutations (R213W,

G272V, G272D, and E551K) modifying highly conserved amino acids of

the protein and a 1 bp frameshift insertion c.[1812_1813insG] were

identified. The missense mutations were introduced into the yeast

ABC1/COQ8 gene and expressed in a Saccharomyces cerevisiae strain in

which the ABC1/COQ8 gene was deleted. All the missense mutations

resulted in a respiratory phenotype with no or decreased growth on

glycerol medium and a severe reduction in ubiquinone synthesis,

demonstrating that these mutations alter the protein function.

PMID: 18319072 [PubMed - indexed for MEDLINE]

- In EOHarm , " sammysouthie " wrote:

>

> The kinetics of enzyme changes in yeast under conditions that cause

> the loss of mitochondria.Chapman C, Bartley W.

> 1. Aerobically grown yeast having a high activity of glyoxylate-

> cycle, citric acid-cycle and electron-transport enzymes was

> transferred to a medium containing 10% glucose. After a lag phase

of

> 30min. the yeast grew exponentially with a mean generation time of

> 94min. 2. The enzymes malate dehydrogenase, isocitrate lyase,

> succinate-cytochrome c oxidoreductase and NADH-cytochrome c

> oxidoreductase lost 45%, 17%, 27% and 46% of their activity

> respectively during the lag phase. 3. When growth commenced

pyruvate

> kinase, pyruvate decarboxylase, alcohol dehydrogenase, glutamate

> dehydrogenase (NADP(+)-linked) and NADPH-cytochrome c

oxidoreductase

> increased in activity, whereas aconitase, isocitrate dehydrogenase

> (NAD(+)- and NADP(+)-linked), alpha-oxoglutarate dehydrogenase,

> fumarase, malate dehydrogenase, succinate-cytochrome c

> oxidoreductase, NADH-cytochrome c oxidoreductase, NADH oxidase,

NADPH

> oxidase, cytochrome c oxidase, glutamate dehydrogenase (NAD(+)-

> linked), glutamate-oxaloacetate transaminase, isocitrate lyase and

> glucose 6-phosphate dehydrogenase decreased. 4. During the early

> stages of growth the loss of activity of aconitase, alpha-

> oxoglutarate dehydrogenase, fumarase and glucose 6-phosphate

> dehydrogenase could be accounted for by dilution by cell division.

> The lower rate of loss of activity of isocitrate dehydrogenase (NAD

> (+)- and NADP(+)-linked), glutamate dehydrogenase (NAD(+)-linked),

> glutamate-oxaloacetate transaminase, NADPH oxidase and cytochrome c

> oxidase implies their continued synthesis, whereas the higher rate

of

> loss of activity of malate dehydrogenase, isocitrate lyase,

succinate-

> cytochrome c oxidoreductase, NADH-cytochrome c oxidoreductase and

> NADH oxidase means that these enzymes were actively removed. 5. The

> mechanisms of selective removal of enzyme activity and the control

of

> the residual metabolic pathways are discussed.

>

> PMID: 5660627 [PubMed - indexed for MEDLINE]

> PMCID: PMC1198688

>

> Inorganic nitrogen assimilation in yeasts: alteration in enzyme

> activities associated with changes in cultural conditions and

growth

> phase.Thomulka KW, Moat AG.

> Ammonia assimilation has been investigated in four strains of

> Saccharomyces cerevisiae by measuring, at intervals throughout the

> growth cycle, the activities of several enzymes concerned with

> inorganic ammonia assimilation. Enzyme activities in extracts of

> cells were compared after growth in complete and defined media. The

> effect of shift from growth in a complete to growth in a defined

> medium (and the reverse) was also determined. The absence of

> aspartase (EC 4.3.1.1, l-aspartate-ammonia lyase) activity, the low

> specific activities of alanine dehydrogenase, glutamine synthetase

> [EC 6.3.1.2, l-glutamate-ammonia ligase (ADP)], and the marked

> increase in activity of the nicotinamide adenine dinucleotide

> phosphate-linked glutamate dehydrogenase (NADP-GDH) [EC 1.4.1.4, l-

> glutamate:NADP-oxidoreductase (deaminating)] during the early

stages

> of growth support the conclusion that yeasts assimilate ammonia

> primarily via glutamate. The NADP-GDH showed a rapid increase in

> activity just before the initiation of exponential growth, reached

a

> maximum at the mid-exponential stage, and then gradually declined

in

> activity in the stationary phase. The NADP-GDH reached a higher

level

> of activity when the yeasts were grown on the defined medium as

> compared with complete medium. The nicotinamide adenine

dinucleotide-

> linked glutamate dehydrogenase (NAD-GDH) [EC 1.4.1.2, l-

glutamate:NAD-

> oxidoreductase (deaminating)] showed only slight increases in

> activity during the exponential phase of growth. There was an

inverse

> relationship in that the NADP-GDH increased in activity as the NAD-

> GDH decreased. The NAD-GDH activity was higher after growth on the

> complete medium. The glutamate-oxaloacetate transaminase (EC

2.6.1.1.

> l-aspartate:2-oxoglutarate aminotransferase) activity rose and fell

> in parallel with the NADP-GDH, although its specific activity was

> somewhat lower. Although other ammonia-assimilatory enzymes were

> demonstrable, it seems unlikely that their combined activities

could

> account for the remainder of the ammonia-assimilatory capacity not

> accounted for by the NADP-GDH. The ability of aspartate to serve as

> effectively as glutamate as the sole source of nitrogen for the

> growth of yeast apparently resides in their ability to utilize

> aspartate for amino acid biosynthesis via transamination.

>

> PMID: 4400414 [PubMed - indexed for MEDLINE]

> PMCID: PMC247247

>

> Promotion of sporulation by caffeine pretreatment in Saccharomyces

> cerevisiae. II. Changes in ribonuclease activity during

> sporulation.Tsuboi M, Yanagishima N.

> Changes in RNase activity during sporulation of a homothallic

diploid

> strain of Saccharomyces cerevisiae were measured in caffeine-

treated

> and non-treated cells. 1. In caffeine-treated cells soon after the

> transfer to the sporulation medium a significant increase in RNase

> activity was observed; in control cells the rise of RNase activity

> was less and started after a lag period of 5 h. The final activity

of

> RNase activity was about twice as high in caffeine-treated cells as

> in control cells. 2. Increase in RNase activity during sporulation

> was sensitive to cycloheximide in control cells, but insensitive in

> caffeine-treated cells. 3. RNases from vegetative cells and from

> sporulating ones are different in their Km values. Relation of the

> changes in RNase activity to premeiotic DNA synthesis is discussed.

>

> PMID: 776113 [PubMed - indexed for MEDLINE]

>