ATP synthase from bovine mitochondria: complementary DNA sequence of the mitochondrial import precursor of the .gamma.-subunit and the genomic sequence of the mature protein

Biochemistry ◽  
1989 ◽  
Vol 28 (9) ◽  
pp. 3670-3680 ◽  
Author(s):  
Mark R. Dyer ◽  
Nicholas J. Gay ◽  
Steven J. Powell ◽  
John E. Walker
Keyword(s):  
Dna Sequence ◽  
Atp Synthase ◽  
Genomic Sequence ◽  
Mature Protein ◽  
Mitochondrial Import ◽  
Gamma Subunit ◽  
Complementary Dna

ATP synthase from bovine mitochondria: complementary DNA sequence of the import precursor of a heart isoform of the .alpha. subunit

Biochemistry ◽  
1989 ◽  
Vol 28 (11) ◽  
pp. 4702-4708 ◽  
Author(s):  
John E. Walker ◽  
Steven J. Powell ◽  
Octavi Vinas ◽  
Michael J. Runswick
Keyword(s):  
Dna Sequence ◽  
Atp Synthase ◽  
Alpha Subunit ◽  
Complementary Dna

scholarly journals DNA sequences of a bovine gene and of two related pseudogenes for the proteolipid subunit of mitochondrial ATP synthase

1989 ◽  
Vol 260 (1) ◽  
pp. 249-258 ◽  
Author(s):  
M R Dyer ◽  
N J Gay ◽  
J E Walker
Keyword(s):  
Dna Sequence ◽  
Atp Synthase ◽  
Dna Sequences ◽  
Genomic Library ◽  
Bovine Genome ◽  
Mitochondrial Import ◽  
Bovine Gene ◽  
Mitochondrial Atp Synthase ◽  
Embryonic Origin ◽  
Dna Sequence Repeats

The dicyclohexylcarbodi-imide-reactive proteolipid is a membrane subunit of mitochondrial ATP synthase. In cows it is encoded by two different nuclear genes known as P1 and P2. These genes are expressed in a tissue-specific fashion which reflects the embryonic origin of the tissues. The proteins that they encode are synthesized in the cytosol, and are precursors of the proteolipid that have different mitochondrial import sequences of 61 and 68 amino acids respectively. By use of gene-specific probes derived from the bovine P2 cDNA, regions containing corresponding parts of the bovine P2 gene have been isolated from a bovine genomic library, and their DNA sequences and those of flanking and intervening regions have been determined. The sequence contains four exons, which represent the cDNA sequence, spread over 3.8 kb of the bovine genome. Two of the introns are in the DNA sequence coding for the mitochondrial import sequence, and a third intron is in a sequence encoding an extramembranous structure between the two putative transmembrane alpha-helical domains of the mature proteolipid. An Alu-type repetitive element was detected at the extreme 5′ end of the sequence. The bovine P1 and P2 genes for the dicyclohexylcarbodimide-reactive proteolipid of ATP synthase are members of a multiple gene family that also contains many pseudogenes. The bovine P1 gene has not been isolated, but two distinct P1 pseudogenes have been cloned and their DNA sequences have been determined. Both of them contain ‘in-phase’ stop codons and frame-shift mutations, and one of them bears the hallmarks of retroposition; it has no introns, it contains a poly(A) tract at its 3′ end and it is flanked by direct DNA sequence repeats. The second P1 pseudogene is very unusual. It appears to be derived from a partially processed transcript and contains an intervening DNA sequence of 861 bp that corresponds in position with an intron in the human P1 gene. This pseudogene also could have been introduced by retroposition since its sequence is flanked by short direct repeats. However, it does not contain a poly(A) tract at its 3′ end. An alternative, but less likely, explanation is that rather than being a retroposon, this sequence arose by duplication of an expressed gene at a time when it had only one intron.

scholarly journals Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase

2021 ◽  
Author(s):  
Marco Fiorillo ◽  
Cristian Scatena ◽  
Antonio Giuseppe Naccarato ◽  
Federica Sotgia ◽  
Michael P. Lisanti
Keyword(s):  
Cell Migration ◽  
Treatment Failure ◽  
Atp Synthase ◽  
Atp Depletion ◽  
Multi Drug Resistance ◽  
Gamma Subunit ◽  
Primary Tumors ◽  
Atp Production ◽  
Mitochondrial Atp Synthase

AbstractHere, we provide evidence that high ATP production by the mitochondrial ATP-synthase is a new therapeutic target for anticancer therapy, especially for preventing tumor progression. More specifically, we isolated a subpopulation of ATP-high cancer cells which are phenotypically aggressive and demonstrate increases in proliferation, stemness, anchorage-independence, cell migration, invasion and multi-drug resistance, as well as high antioxidant capacity. Clinically, these findings have important implications for understanding treatment failure and cancer cell dormancy. Using bioinformatic analysis of patient samples, we defined a mitochondrial-related gene signature for metastasis, which features the gamma-subunit of the mitochondrial ATP-synthase (ATP5F1C). The relationship between ATP5F1C protein expression and metastasis was indeed confirmed by immunohistochemistry. Next, we used MDA-MB-231 cells as a model system to functionally validate these findings. Importantly, ATP-high MDA-MB-231 cells showed a nearly fivefold increase in metastatic capacity in vivo. Consistent with these observations, ATP-high cells overexpressed (i) components of mitochondrial complexes I–V, including ATP5F1C, and (ii) markers associated with circulating tumor cells (CTCs) and metastasis, such as EpCAM and VCAM1. Knockdown of ATP5F1C expression significantly reduced ATP-production, anchorage-independent growth, and cell migration, as predicted. Similarly, therapeutic administration of the FDA-approved drug, Bedaquiline, downregulated ATP5F1C expression in vitro and prevented spontaneous metastasis in vivo. In contrast, Bedaquiline had no effect on the growth of non-tumorigenic mammary epithelial cells (MCF10A) or primary tumors in vivo. Taken together, our results suggest that mitochondrial ATP depletion is a new therapeutic strategy for metastasis prophylaxis, to avoid treatment failure. In summary, we conclude that mitochondrial ATP5F1C is a promising new biomarker and molecular target for future drug development, for the prevention of metastatic disease progression.

scholarly journals Investigation of the molecular signatures of selection on ATP synthase genes in the marine bivalve Limecola balthica

2019 ◽  
Vol 32 ◽  
pp. 3 ◽  
Author(s):  
Eric Pante ◽  
Vanessa Becquet ◽  
Amélia Viricel ◽  
Pascale Garcia
Keyword(s):  
Atp Synthase ◽  
Sequence Data ◽  
Nuclear Gene ◽  
Cellular Respiration ◽  
Marine Bivalve ◽  
Gamma Subunit ◽  
Genetic Barriers ◽  
Different Populations ◽  
Peptide Interaction ◽  
Evolutionarily Stable

We used transcriptomic sequence data to describe patterns of divergence and selection across different populations of a marine bivalve (Limecola balthica). Our analyses focused on a nuclear gene (atp5c1) that was previously detected in an FST scan as highly structured among populations separated by the Finistère Peninsula in France. This gene encodes the gamma subunit of the FO/F1 ATP synthase, a multi-protein complex that is paramount to cellular respiration and energy production. Analysis of non-synonymous to synonymous mutation ratios revealed that 65% of the gene is highly conserved (dN/dS ≤ 0.1, min = 0), while 6% of the gene is likely under positive selection (dN/dS ≥ 1, max = 2.03). All replacement mutations are clustered on a 46 residues portion of the protein, within an inter-peptide interaction zone. Comparative genomics suggests that these mutations are evolutionarily stable, and we hypothesize that they are involved in inter-population genetic incompatibilities with other subunits of the ATP synthase complex. The protein stability of the gamma subunit conferred by southern variants was inferred to be higher under warmer temperatures, suggesting that environmental conditions may contribute to the strength of genetic barriers in L. balthica.

scholarly journals NADH:ubiquinone oxidoreductase from bovine heart mitochondria Complementary DNA sequence of the import precursor of the 10 kDa subunit of the flavoprotein fragment

FEBS Letters ◽  
1991 ◽  
Vol 282 (1) ◽  
pp. 135-138 ◽  
Author(s):  
J.Mark Skehel ◽  
Stephanie J. Pilkington ◽  
Michael J. Runswick ◽  
Ian M. Fearnley ◽  
John E. Walker
Keyword(s):  
Dna Sequence ◽  
Heart Mitochondria ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Complementary Dna ◽  
Bovine Heart

Complementary DNA sequence of rabbit CAP18—A unique lipopolysaccharide binding protein

1991 ◽  
Vol 179 (1) ◽  
pp. 170-175 ◽  
Author(s):  
James W. Larrick ◽  
John G. Morgan ◽  
Ilona Palings ◽  
Michimasa Hirata ◽  
Michael H. Yen
Keyword(s):  
Dna Sequence ◽  
Binding Protein ◽  
Lipopolysaccharide Binding Protein ◽  
Complementary Dna ◽  
Lipopolysaccharide Binding

scholarly journals Phylogenetic analysis of a reported complementary DNA sequence

Science ◽  
1994 ◽  
Vol 265 (5175) ◽  
pp. 1110-1111 ◽  
Author(s):  
E Zietkiewicz ◽  
W Makalowski ◽  
G. Mitchell ◽  
D Labuda
Keyword(s):  
Phylogenetic Analysis ◽  
Dna Sequence ◽  
Complementary Dna
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