scholarly journals stress sensitive B Encodes an Adenine Nucleotide Translocase in Drosophila melanogaster

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 891-903 ◽  
Author(s):  
Yong Q Zhang ◽  
John Roote ◽  
Saverio Brogna ◽  
Andrew W Davis ◽  
Daniel A Barbash ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Sibling Species ◽  
Interspecific Hybrids ◽  
Mitochondrial Membrane ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Translocase ◽  
Differential Splicing ◽  
Inner Mitochondrial Membrane

Abstract Adenine nucleotide translocases (ANT) are required for the exchange of ADP and ATP across the inner mitochondrial membrane. They are essential for life, and most eukaryotes have at least two different Ant genes. Only one gene had been described from Drosophila, and this had not been characterized genetically. We show that mutations in this gene correspond to the previously described loci, sesB and l(1)9Ed. Immediately adjacent to this gene is another encoding a second ANT protein, which has 78% identity to that encoded by sesB/l(1)9Ed. These two genes are transcribed from a common promoter, and their mRNAs are produced by differential splicing. Hutter and Karch suggested that the sesB ANT gene corresponded to Hmr, a gene identified by an allele that rescues otherwise inviable interspecific hybrids between Drosophila melanogaster and its sibling species. This hypothesis is not supported by our study of the ANT genes of D. melanogaster.

scholarly journals Adenine Nucleotide Translocase 1 Expression Is Coupled to the HSP27-Mediated TLR4 Signaling in Cardiomyocytes

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1588 ◽  
Author(s):  
Julia Winter ◽  
Elke Hammer ◽  
Jacqueline Heger ◽  
Heinz-Peter Schultheiss ◽  
Ursula Rauch ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Adenine Nucleotide ◽  
Heart Tissue ◽  
Neonatal Rat ◽  
Adenine Nucleotide Translocase ◽  
Inner Mitochondrial Membrane ◽  
Tlr4 Signaling ◽  
Rat Cardiomyocytes

The cardiac-specific overexpression of the adenine nucleotide translocase 1 (ANT1) has cardioprotective effects in various experimental heart disease models. Here, we analyzed the link between ANT1 expression and heat shock protein 27 (HSP27)-mediated toll-like receptor 4 (TLR4) signaling, which represents a novel communication pathway between mitochondria and the extracellular environment. The interaction between ANT1 and HSP27 was identified by co-immunoprecipitation from neonatal rat cardiomyocytes. ANT1 transgenic (ANT1-TG) cardiomyocytes demonstrated elevated HSP27 expression levels. Increased levels of HSP27 were released from the ANT1-TG cardiomyocytes under both normoxic and hypoxic conditions. Extracellular HSP27 stimulated TLR4 signaling via protein kinase B (AKT). The HSP27-mediated activation of the TLR4 pathway was more pronounced in ANT1-TG cardiomyocytes than in wild-type (WT) cardiomyocytes. HSP27-specific antibodies inhibited TLR4 activation and the expression of HSP27. Inhibition of the HSP27-mediated TLR4 signaling pathway with the TLR4 inhibitor oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) reduced the mitochondrial membrane potential (∆ψm) and increased caspase 3/7 activity, which are both markers for cell stress. Conversely, treating cardiomyocytes with recombinant HSP27 protein stimulated TLR4 signaling, induced HSP27 and ANT1 expression, and stabilized the mitochondrial membrane potential. The activation of HSP27 signaling was verified in ischemic ANT1-TG heart tissue, where it correlated with ANT1 expression and the tightness of the inner mitochondrial membrane. Our study shows a new mechanism by which ANT1 is part of the cardioprotective HSP27-mediated TLR4 signaling.

scholarly journals The Role of Adenine Nucleotide Translocase in the Mitochondrial Permeability Transition

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2686
Author(s):  
Nickolay Brustovetsky
Keyword(s):  
Atp Synthase ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Adenine Nucleotide ◽  
Permeability Transition ◽  
Adenine Nucleotide Translocase ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Permeability ◽  
F0f1 Atp Synthase

The mitochondrial permeability transition, a Ca2+-induced significant increase in permeability of the inner mitochondrial membrane, plays an important role in various pathologies. The mitochondrial permeability transition is caused by induction of the permeability transition pore (PTP). Despite significant effort, the molecular composition of the PTP is not completely clear and remains an area of hot debate. The Ca2+-modified adenine nucleotide translocase (ANT) and F0F1 ATP synthase are the major contenders for the role of pore in the PTP. This paper briefly overviews experimental results focusing on the role of ANT in the mitochondrial permeability transition and proposes that multiple molecular entities might be responsible for the conductance pathway of the PTP. Consequently, the term PTP cannot be applied to a single specific protein such as ANT or a protein complex such as F0F1 ATP synthase, but rather should comprise a variety of potential contributors to increased permeability of the inner mitochondrial membrane.

scholarly journals ADENINE NUCLEOTIDE-INDUCED CONTRACTION OF THE INNER MITOCHONDRIAL MEMBRANE

1973 ◽  
Vol 56 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Clinton D. Stoner ◽  
Howard D. Sirak
Keyword(s):  
Binding Sites ◽  
Mitochondrial Membrane ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Nucleotide Binding ◽  
Nucleotide Exchange ◽  
Inner Mitochondrial Membrane ◽  
Inner Membrane ◽  
Nucleotide Binding Sites ◽  
Bongkrekic Acid

In bovine heart mitochondria bongkrekic acid at concentrations as low as about 4 nmol/mg protein (a) completely inhibits phosphorylation of exogenous adenosine diphosphate (ADP) and dephosphorylation of exogenous adenosine triphosphate (ATP), (b) completely reverses atractyloside inhibition of inner membrane contraction induced by exogenous adenine nucleotides, and (c) decreases the amount of adenine nucleotide required to elicit maximal exogenous adenine nucleotide-induced inner membrane contraction to a level which appears to correspond closely with the concentration of contractile, exogenous adenine nucleotide binding sites Bongkrekic acid at concentrations greater than 4 nmol/mg protein induces inner membrane contraction which seems to depend on the presence of endogenous ADP and/or ATP. The findings appear to be consistent with the interpretations (a) that the inner mitochondrial membrane contains two types of contractile, adenine nucleotide binding sites, (b) that the two sites differ markedly with regard to adenine nucleotide affinity, (c) that the high affinity site is identical with the adenine nucleotide exchange carrier, (d) that the low affinity site is accessible exclusively to endogenous adenine nucleotides and is largely unoccupied in the absence of bongkrekic acid, and (e) that bongkrekic acid increases the affinity of both sites in proportion to the amount of the antibiotic bound to the inner membrane.

scholarly journals The Role of Adenine Nucleotide Translocase in the Assembly of Respiratory Supercomplexes in Cardiac Cells

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1247 ◽  
Author(s):  
Rebecca M. Parodi-Rullán ◽  
Xavier Chapa-Dubocq ◽  
Roberto Guzmán-Hernández ◽  
Sehwan Jang ◽  
Carlos A. Torres-Ramos ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Adenine Nucleotide ◽  
Physiological Role ◽  
Cardiac Cells ◽  
Adenine Nucleotide Translocase ◽  
Inner Mitochondrial Membrane ◽  
Chain Complexes ◽  
Transport Chain ◽  
H9c2 Cardiomyoblasts

Individual electron transport chain complexes have been shown to assemble into the supramolecular structures known as the respiratory chain supercomplexes (RCS). Several studies reported an associative link between RCS disintegration and human diseases, although the physiological role, structural integrity, and mechanisms of RCS formation remain unknown. Our previous studies suggested that the adenine nucleotide translocase (ANT), the most abundant protein of the inner mitochondrial membrane, can be involved in RCS assembly. In this study, we sought to elucidate whether ANT knockdown (KD) affects RCS formation in H9c2 cardiomyoblasts. Results showed that genetic silencing of ANT1, the main ANT isoform in cardiac cells, stimulated proliferation of H9c2 cardiomyoblasts with no effect on cell viability. ANT1 KD reduced the ΔΨm but increased total cellular ATP levels and stimulated the production of total, but not mitochondrial, reactive oxygen species. Importantly, downregulation of ANT1 had no significant effects on the enzymatic activity of individual ETC complexes I–IV; however, RCS disintegration was stimulated in ANT1 KD cells as evidenced by reduced levels of respirasome, the main RCS. The effects of ANT1 KD to induce RCS disassembly was not associated with acetylation of the exchanger. In conclusion, our study demonstrates that ANT is involved in RCS assembly.

scholarly journals Adenine Nucleotide Translocase-1, a Component of the Permeability Transition Pore, Can Dominantly Induce Apoptosis

1999 ◽  
Vol 147 (7) ◽  
pp. 1493-1502 ◽  
Author(s):  
Manuel K.A. Bauer ◽  
Alexis Schubert ◽  
Oliver Rocks ◽  
Stefan Grimm
Keyword(s):  
Cell Death ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Adenine Nucleotide ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Adenine Nucleotide Translocase ◽  
Cyclophilin D ◽  
Protein Aggregate ◽  
Cytochrome C Release

Here, we describe the isolation of adenine nucleotide translocase-1 (ANT-1) in a screen for dominant, apoptosis-inducing genes. ANT-1 is a component of the mitochondrial permeability transition complex, a protein aggregate connecting the inner with the outer mitochondrial membrane that has recently been implicated in apoptosis. ANT-1 expression led to all features of apoptosis, such as phenotypic alterations, collapse of the mitochondrial membrane potential, cytochrome c release, caspase activation, and DNA degradation. Both point mutations that impair ANT-1 in its known activity to transport ADP and ATP as well as the NH2-terminal half of the protein could still induce apoptosis. Interestingly, ANT-2, a highly homologous protein could not lead to cell death, demonstrating the specificity of the signal for apoptosis induction. In contrast to Bax, a proapoptotic Bcl-2 gene, ANT-1 was unable to elicit a form of cell death in yeast. This and the observed repression of apoptosis by the ANT-1–interacting protein cyclophilin D suggest that the suicidal effect of ANT-1 is mediated by specific protein–protein interactions within the permeability transition pore.

scholarly journals ANT1 Activation and Inhibition Patterns Support the Fatty Acid Cycling Mechanism for Proton Transport

2021 ◽  
Vol 22 (5) ◽  
pp. 2490
Author(s):  
Jürgen Kreiter ◽  
Anne Rupprecht ◽  
Sanja Škulj ◽  
Zlatko Brkljača ◽  
Kristina Žuna ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Bilayers ◽  
Proton Transport ◽  
Mitochondrial Membrane ◽  
Adenine Nucleotide ◽  
Molecular Transport ◽  
Correlation Spectroscopy ◽  
Dual Function ◽  
Inner Mitochondrial Membrane ◽  
Purine Nucleotides

Adenine nucleotide translocase (ANT) is a well-known mitochondrial exchanger of ATP against ADP. In contrast, few studies have shown that ANT also mediates proton transport across the inner mitochondrial membrane. The results of these studies are controversial and lead to different hypotheses about molecular transport mechanisms. We hypothesized that the H+-transport mediated by ANT and uncoupling proteins (UCP) has a similar regulation pattern and can be explained by the fatty acid cycling concept. The reconstitution of purified recombinant ANT1 in the planar lipid bilayers allowed us to measure the membrane current after the direct application of transmembrane potential ΔΨ, which would correspond to the mitochondrial states III and IV. Experimental results reveal that ANT1 does not contribute to a basal proton leak. Instead, it mediates H+ transport only in the presence of long-chain fatty acids (FA), as already known for UCPs. It depends on FA chain length and saturation, implying that FA’s transport is confined to the lipid-protein interface. Purine nucleotides with the preference for ATP and ADP inhibited H+ transport. Specific inhibitors of ATP/ADP transport, carboxyatractyloside or bongkrekic acid, also decreased proton transport. The H+ turnover number was calculated based on ANT1 concentration determined by fluorescence correlation spectroscopy and is equal to 14.6 ± 2.5 s−1. Molecular dynamic simulations revealed a large positively charged area at the protein/lipid interface that might facilitate FA anion’s transport across the membrane. ANT’s dual function—ADP/ATP and H+ transport in the presence of FA—may be important for the regulation of mitochondrial membrane potential and thus for potential-dependent processes in mitochondria. Moreover, the expansion of proton-transport modulating drug targets to ANT1 may improve the therapy of obesity, cancer, steatosis, cardiovascular and neurodegenerative diseases.

scholarly journals ADENINE NUCLEOTIDE-INDUCED CONTRACTION OF THE INNER MITOCHONDRIAL MEMBRANE

1973 ◽  
Vol 56 (1) ◽  
pp. 51-64 ◽  
Author(s):  
Clinton D. Stoner ◽  
Howard D. Sirak
Keyword(s):  
Mitochondrial Membrane ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Mitochondrial Protein ◽  
Adenosine Diphosphate ◽  
High Energy ◽  
Maximal Contraction ◽  
High Energy Phosphate ◽  
Inner Mitochondrial Membrane ◽  
Inner Membrane

The inner membranes of isolated bovine heart mitochondria undergo pronounced contraction upon being exposed to exogenous adenosine diphosphate (ADP), adenosine triphosphate (ATP), and certain other high-energy phosphate compounds. Contraction results in decrease of inner membrane expanse which in turn results in decrease of intracristal space and increase of mitochondrial optical density (OD). The magnitude of the OD change appears to be proportional to the degree of contraction Half-maximal contraction can be achieved with ADP or ATP at concentrations as low as about 0 3 µM. Atractyloside at concentrations as low as about 1.2 nmol/mg mitochondrial protein completely inhibits the contraction. It is concluded from these and other observations that inner membrane contraction occurs as a result of adenine nucleotide binding to the carrier involved in the exchange of adenine nucleotides across the inner mitochondrial membrane.

scholarly journals Mitochondria Isolated from Hearts Subjected to Ischemia/Reperfusion Benefit from Adenine Nucleotide Translocase 1 Overexpression

Membranes ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 836
Author(s):  
Andrea Dörner ◽  
Oleg Lynetskiy ◽  
Gerhild Euler ◽  
Ulf Landmesser ◽  
Klaus-Dieter Schlüter ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Diastolic Function ◽  
Mitochondrial Function ◽  
Diastolic Pressure ◽  
Adenine Nucleotide ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Adenine Nucleotide Translocase ◽  
Inner Mitochondrial Membrane ◽  
Rat Hearts

Reperfusion is the only feasible therapy following myocardial infarction, but reperfusion has been shown to damage mitochondrial function and disrupt energy production in the heart. Adenine nucleotide translocase 1 (ANT1) facilitates the transfer of ADP/ATP across the inner mitochondrial membrane; therefore, we tested whether ANT1 exerts protective effects on mitochondrial function during ischemia/reperfusion (I/R). The hearts of wild-type (WT) and transgenic ANT1-overexpressing (ANT1-TG) rats were exposed to I/R injury using the standard Langendorff technique, after which mitochondrial function, hemodynamic parameters, infarct size, and components of the contractile apparatus were determined. ANT1-TG hearts expressed higher ANT protein levels, with reduced levels of oxidative 4-hydroxynonenal ANT modifications following I/R. ANT1-TG mitochondria isolated from I/R hearts displayed stable calcium retention capacity (CRC) and improved membrane potential stability compared with WT mitochondria. Mitochondria isolated from ANT1-TG hearts experienced less restricted oxygen consumption than WT mitochondria after I/R. Left ventricular diastolic pressure (Pdia) decreased in ANT1-TG hearts compared with WT hearts following I/R. Preserved diastolic function was accompanied by a decrease in the phospho-lamban (PLB)/sarcoplasmic reticulum calcium ATPase (SERCA2a) ratio in ANT1-TG hearts compared with that in WT hearts. In addition, the phosphorylated (P)-PLB/PLB ratio increased in ANT1-TG hearts after I/R but not in WT hearts, which indicated more effective calcium uptake into the sarcoplasmic reticulum in ANT1-TG hearts. In conclusion, ANT1-TG rat hearts coped more efficiently with I/R than WT rat hearts, which was reflected by preserved mitochondrial energy balance, diastolic function, and calcium dynamics after reperfusion.

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