Gene Expression of Subunit c(P1), Subunit c(P2), and Oligomycin Sensitivity-conferring Protein May Play a Key Role in Biogenesis of H+-ATP Synthase in Various Rat Tissues

Sangawa, Hidehiro; Himeda, Toshiki; Shibata, Hirofumi; Higuti, Tomihiko

doi:10.1074/jbc.272.9.6034

Cited by 28 publications

(32 citation statements)

References 35 publications

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“…In this context, it is noteworthy that there are differences in brain and muscle in the expression of isoforms of subunit c with which A6 interacts (35). Furthermore, IF 1 is expressed at relatively high levels in developing rat brain compared with muscle (36). This observation suggests that ATP hydrolysis needs to be strictly controlled in developing brain and thereby offers an explanation of how increased levels of sub-complexes of complex V resulting from the presence of the T8993G mtDNA mutation might cause tissue-specific metabolic failure.…”

Section: Discussionmentioning

confidence: 99%

Impaired ATP Synthase Assembly Associated with a Mutation in the Human ATP Synthase Subunit 6 Gene

Nijtmans

Henderson

Attardi

et al. 2001

Journal of Biological Chemistry

110

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Mutations in human mitochondrial DNA are a well recognized cause of disease. A mutation at nucleotide position 8993 of human mitochondrial DNA, located within the gene for ATP synthase subunit 6, is associated with the neurological muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome. To enable analysis of this mutation in control nuclear backgrounds, two different cell lines were transformed with mitochondria carrying NARP mutant mitochondrial DNA. Transformant cell lines had decreased ATP synthesis capacity, and many also had abnormally high levels of two ATP synthase sub-complexes, one of which was F 1 -ATPase. A combination of metabolic labeling and immunoblotting experiments indicated that assembly of ATP synthase was slowed and that the assembled holoenzyme was unstable in cells carrying NARP mutant mitochondrial DNA compared with control cells. These findings indicate that altered assembly and stability of ATP synthase are underlying molecular defects associated with the NARP mutation in subunit 6 of ATP synthase, yet intrinsic enzyme activity is also compromised.

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Section: Discussionmentioning

confidence: 99%

Impaired ATP Synthase Assembly Associated with a Mutation in the Human ATP Synthase Subunit 6 Gene

Nijtmans

Henderson

Attardi

et al. 2001

Journal of Biological Chemistry

110

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“…As described previously [20], the probes used were a XhoI± BglII fragment of the cDNA for subunit b [21], an AccI±AvaI fragment of cDNA for subunit d [22], a HindIII±HindIII fragment of cDNA for subunit e [23], a HindIII±ApaLI fragment of cDNA for OSCP [24], a HindIII±ApaLI fragment of cDNA for IF1 [24], a HindIII±HindIII fragment of cDNA for F6 [25], a…”

Section: P-labeled Probe Dnasmentioning

confidence: 99%

Synchronized transcriptional gene expression of H+-ATP synthase subunits in different tissues of Fischer 344 rats of different ages

Himeda¹,

Morokami²,

Arakaki³

et al. 2000

Eur J Biochem

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Little is known about the relationship between the stoichiometry of polypeptides of multisubunit enzyme complexes and the absolute amount of each transcript of the complexes in mammalian tissues. Here we showed that the absolute amounts of the transcripts of most subunits of rat H 1 -ATP synthase examined greatly differed in the different tissues, showing the following hierarchy of tissue-specificity: heart . kidney . brain < liver. However, surprisingly, there was no difference in the expression pattern of these in terms of the molar ratio of each transcript, indicating a nearly similar stoichiometric expression pattern irrespective of tissue or age of the rat. Therefore, the present finding clearly indicates that most of the transcripts of the 16 subunits of rat H 1 -ATP synthase were concertedly and synchronously expressed, having a constant expression pattern of the transcripts, irrespective of tissue or age of the rats. This is the first report of the absolute amounts of the transcripts of this multisubunit enzyme.Keywords: H 1 -ATP synthase; expression pattern; transcript; stoichiometry; synchronization.The mechanism of the transcriptional regulation of the genes involved in the biosynthesis and assembly of multisubunit mitochondrial enzyme complexes, e.g. [14,17±18a]. Subunit a and A6L are encoded by the mitochondrial genome, and all of the other subunits are separately encoded by nuclear chromosomes; however, the relationship between the stoichiometry of polypeptides of the complexes and the absolute amount of each transcript of this multisubunit enzyme complex in mammalian tissues is still entirely unknown.In the present work, we determined the absolute amount of nine species of mRNAs for eight nucleus-encoded subunits of H 1 -ATP synthase in the brain, liver, heart, and kidney tissues of 2-week-old to 90-week-old male Fischer 344 rats by using highly purified poly(A) 1 RNA and the mRNAs synthesized by an in vitro transcriptional system. M A T E R I A L S A N D M E T H O D S AnimalsMale Fischer 344 rats were obtained from Charles River Japan Inc (Atsugi, Japan), and were genetically identical because of approximately 300 matings between sister and brother. Purification of Poly(A)1 RNAThe rats were decapitated, and tissues of brain, liver, heart, and kidney were rapidly removed. Total RNA from these tissues was isolated by the guanidinium thiocyanate method [19], followed by centrifugation at 120 000 g for 24 h in 5.7 m CsCl solution and then extraction with acid phenol. The poly(A) 1 RNA was purified with Oligotex-dT30 (Takara) according to the manufacturer's instructions, and the purification steps with Oligotex-dT30 were repeated twice. The poly(A) 1 RNA eluted from the 2nd Oligotex-dT30 was extracted with acid phenol, precipitated with 70% ethanol, dried, and dissolved in diethyl pyrocarbonate-treated water. The amount of poly(A) 1 RNA was determined from the absorbance at 260 nm (one unit of absorbance at 260 nm 40 mg´mL 21). The A260/A280 ratios were in the range 1.8±2.0. Contamination by ribosoma...

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“…In brown fat a selective transcriptional down-regulation of subunit c isogenes P1 and P2 and availability of the subunit c has been found as a limiting step for de novo synthesis of ATPase [35]. The transcriptional control of subunit c genes has been implicated in control of the cellular content of ATPase also in other mammalian tissues [36,37]. However, in ATPase-deficient patients expression of subunit c isogenes was normal or even increased [27] and the mRNA levels for other ATPase subunits did not show a significant decrease.…”

Section: F 1 -Atpase Assembly and Affected Nuclear Factor(s)mentioning

confidence: 99%

Mitochondrial diseases and ATPase defects of nuclear origin

Houštěk

Mráček

Vojtíšková

et al. 2004

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Dysfunctions of the F(1)F(o)-ATPase complex cause severe mitochondrial diseases affecting primarily the paediatric population. While in the maternally inherited ATPase defects due to mtDNA mutations in the ATP6 gene the enzyme is structurally and functionally modified, in ATPase defects of nuclear origin mitochondria contain a decreased amount of otherwise normal enzyme. In this case biosynthesis of ATPase is down-regulated due to a block at the early stage of enzyme assembly-formation of the F(1) catalytic part. The pathogenetic mechanism implicates dysfunction of Atp12 or other F(1)-specific assembly factors. For cellular energetics, however, the negative consequences may be quite similar irrespective of whether the ATPase dysfunction is of mitochondrial or nuclear origin.

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Gene Expression of Subunit c(P1), Subunit c(P2), and Oligomycin Sensitivity-conferring Protein May Play a Key Role in Biogenesis of H+-ATP Synthase in Various Rat Tissues

Cited by 28 publications

References 35 publications

Impaired ATP Synthase Assembly Associated with a Mutation in the Human ATP Synthase Subunit 6 Gene

Impaired ATP Synthase Assembly Associated with a Mutation in the Human ATP Synthase Subunit 6 Gene

Synchronized transcriptional gene expression of H+-ATP synthase subunits in different tissues of Fischer 344 rats of different ages

Mitochondrial diseases and ATPase defects of nuclear origin

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