Two genes encoding the bovine mitochondrial ATP synthase proteolipid specify precursors with different import sequences and are expressed in a tissue-specific manner.

Human diseases range from gene-associated to gene-non-associated disorders, including age-related diseases, neurodegenerative, neuromuscular, cardiovascular, diabetic diseases, neurocognitive disorders and cancer. Mitochondria participate to the cascades of pathogenic events leading to the onset and progression of these diseases independently of their association to mutations of genes encoding mitochondrial protein. Under physiological conditions, the mitochondrial ATP synthase provides the most energy of the cell via the oxidative phosphorylation. Alterations of oxidative phosphorylation mainly affect the tissues characterized by a high-energy metabolism, such as nervous, cardiac and skeletal muscle tissues. In this review, we focus on human diseases caused by altered expressions of ATP synthase genes of both mitochondrial and nuclear origin. Moreover, we describe the contribution of ATP synthase to the pathophysiological mechanisms of other human diseases such as cardiovascular, neurodegenerative diseases or neurocognitive disorders.

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Expression of Bovine F1-ATPase with Functional Complementation in Yeast Saccharomyces cerevisiae

Journal of Biological Chemistry ◽

10.1074/jbc.m411113200 ◽

2005 ◽

Vol 280 (23) ◽

pp. 22418-22424 ◽

Cited By ~ 8

Author(s):

Neeti Puri ◽

Jie Lai-Zhang ◽

Scott Meier ◽

David M. Mueller

Keyword(s):

Saccharomyces Cerevisiae ◽

Molecular Mass ◽

Atp Synthase ◽

Specific Activity ◽

Functional Complementation ◽

Yeast Saccharomyces Cerevisiae ◽

F1 Atpase ◽

Mitochondrial Atp Synthase ◽

Genes Encoding ◽

Molecular Machinery

The mitochondrial F1F0-ATP synthase is a multimeric enzyme complex composed of at least 16 unique peptides with an overall molecular mass of ∼600 kDa. F1-ATPase is composed of α3β3γδϵ with an overall molecular mass of 370 kDa. The genes encoding bovine F1-ATPase have been expressed in a quintuple yeast Saccharomyces cerevisiae deletion mutant (ΔαΔβΔγΔδΔϵ). This strain expressing bovine F1 is unable to grow on medium containing a non-fermentable carbon source (YPG), indicating that the enzyme is non-functional. However, daughter strains were easily selected for growth on YPG medium and these were evolved for improved growth on YPG medium. The evolution of the strains was presumably due to mutations, but mutations in the genes encoding the subunits of the bovine F1-ATPase were not required for the ability of the cell to grow on YPG medium. The bovine enzyme expressed in yeast was partially purified to a specific activity of about half of that of the enzyme purified from bovine heart mitochondria. These results indicate that the molecular machinery required for the assembly of the mitochondrial ATP synthase is conserved from bovine and yeast and suggest that yeast may be useful for the expression, mutagenesis, and analysis of the mammalian F1- or F1F0-ATP synthase.

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Identification of cryptic subunits from an apicomplexan ATP synthase

eLife ◽

10.7554/elife.38097 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 14

Author(s):

Diego Huet ◽

Esther Rajendran ◽

Giel G van Dooren ◽

Sebastian Lourido

Keyword(s):

Oxygen Consumption ◽

Toxoplasma Gondii ◽

Atp Synthase ◽

Proton Gradient ◽

Mitochondrial Morphology ◽

Apicomplexan Parasites ◽

Essential Component ◽

Mitochondrial Atp Synthase ◽

Form Part ◽

Genes Encoding

The mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Modeling suggests that two of them, ICAP2 and ICAP18, are distantly related to mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.

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Sequencing and analysis of Arabidopsis thaliana NOR2 reveal its distinct organization and tissue-specific expression of rRNA ribosomal variants

10.1101/2020.09.10.272005 ◽

2020 ◽

Author(s):

Jason Sims ◽

Giovanni Sestini ◽

Christiane Elgert ◽

Arndt von Haeseler ◽

Peter Schlögelhofer

Keyword(s):

Rrna Gene ◽

Sequence Information ◽

Specific Expression ◽

Rdna Genes ◽

Tissue Specific ◽

Short Read Sequencing ◽

Sequencing Technologies ◽

Nucleolus Organizing Region ◽

Specific Manner ◽

Genes Encoding

AbstractDespite vast differences between organisms, some characteristics of their genomes are conserved, such as the nucleolus organizing region (NOR). The NOR is constituted of multiple, highly repetitive rDNA genes, encoding the catalytic ribosomal core RNAs which are transcribed from 45S rDNA units. Their precise sequence information and organization remained uncharacterized.We used a combination of long- and short-read sequencing technologies to assemble contigs of the Arabidopsis NOR2 rDNA domain providing a first map. We identified several expressed rRNA gene variants which are integrated into translating ribosomes in a tissue-specific manner. These findings support the concept of tissue specific ribosome subpopulations that differ in their rRNA composition and provide the higher order organization of NOR2.

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Sequencing of the Arabidopsis NOR2 reveals its distinct organization and tissue-specific rRNA ribosomal variants

Nature Communications ◽

10.1038/s41467-020-20728-6 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Jason Sims ◽

Giovanni Sestini ◽

Christiane Elgert ◽

Arndt von Haeseler ◽

Peter Schlögelhofer

Keyword(s):

Rrna Gene ◽

Sequence Information ◽

45S Rdna ◽

Rdna Genes ◽

Tissue Specific ◽

Short Read Sequencing ◽

Sequencing Technologies ◽

Nucleolus Organizing Region ◽

Specific Manner ◽

Genes Encoding

AbstractDespite vast differences between organisms, some characteristics of their genomes are conserved, such as the nucleolus organizing region (NOR). The NOR is constituted of multiple, highly repetitive rDNA genes, encoding the catalytic ribosomal core RNAs which are transcribed from 45S rDNA units. Their precise sequence information and organization remain uncharacterized. Here, using a combination of long- and short-read sequencing technologies we assemble contigs of the Arabidopsis NOR2 rDNA domain. We identify several expressed rRNA gene variants which are integrated into translating ribosomes in a tissue-specific manner. These findings support the concept of tissue specific ribosome subpopulations that differ in their rRNA composition and provide insights into the higher order organization of NOR2.

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Structures of the genes encoding the α and β subunits of the Neurospora crassa mitochondrial ATP synthase

Gene ◽

10.1016/0378-1119(92)90569-b ◽

1992 ◽

Vol 114 (2) ◽

pp. 157-163 ◽

Cited By ~ 11

Author(s):

Emma Jean Bowman ◽

Tracey E. Knock

Keyword(s):

Neurospora Crassa ◽

Atp Synthase ◽

Mitochondrial Atp Synthase ◽

Genes Encoding ◽

Α And Β Subunits

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Identification of cryptic stator subunits from an apicomplexan ATP synthase

10.1101/314385 ◽

2018 ◽

Cited By ~ 2

Author(s):

Diego Huet ◽

Esther Rajendran ◽

Giel G. Van Dooren ◽

Sebastian Lourido

Keyword(s):

Oxygen Consumption ◽

Atp Synthase ◽

Hidden Markov ◽

Mitochondrial Morphology ◽

Markov Modeling ◽

Apicomplexan Parasites ◽

Hidden Markov Modeling ◽

Mitochondrial Atp Synthase ◽

Form Part ◽

Genes Encoding

ABSTRACTThe mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Hidden Markov modeling suggests that two of them—ICAP2 and ICAP18—share distant homology with mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.

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