scholarly journals Palmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca2+ leak in cardiomyocytes: Role of adenine nucleotide translocase

2015 ◽  
Vol 1852 (5) ◽  
pp. 749-758 ◽  
Author(s):  
J. Roussel ◽  
J. Thireau ◽  
C. Brenner ◽  
N. Saint ◽  
V. Scheuermann ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Translocase ◽  
Palmitoyl Carnitine

Cardiac expression of adenine nucleotide translocase-1 in transgenic mice overexpressing bovine GH

2007 ◽  
Vol 194 (3) ◽  
pp. 521-527 ◽  
Author(s):  
Fausto Bogazzi ◽  
Francesco Raggi ◽  
Federica Ultimieri ◽  
Dania Russo ◽  
Antonella Manariti ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Transgenic Mice ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Translocase ◽  
Common Finding ◽  
Atp Production ◽  
Tissue Levels ◽  
Atp Generation ◽  
Gh Excess

Heart hypertrophy is a common finding of acromegaly, a syndrome due to GH excess. Impairment of adenine nucleotide translocase-1 (ANT-1) gene, the main mitochondrial ADP/ATP exchanger, leads to cardiac hypertrophy. The aim of the study was to evaluate cardiac expression and the functional role of ANT-1 in 1- to 12-month-old transgenic mice overexpressing bovine GH (acromegalic mice, Acro) and littermate controls (wild-type mice, Wt). GH specificity of protein degree variation was assessed treating Acro with pegvisomant, a GH receptor competitor. Tissue levels of ANT-1, NF-κB, ATP, and lactic acid were evaluated by western blot, bioluminescence, and Fourier transform infrared spectroscopy respectively. The degree of ANT-1 expression was higher in 1-month-old Acro than in Wt (47±5% OD vs 33±4% OD, P<0 01). On the contrary, ANT-1 expression was lower in 3- to 12-month-old Acro than in Wt (P<0 03). Changes in ANT-1 expression were associated with consistent changes of cellular ATP content, increasing at 1 month (P<0 05) and reducing thereafter in Acro when compared with Wt (P<0 04). Treatment with pegvisomant abolished ANT-1 and ATP changes observed in 1- and 3-month-old Acro, thus supporting a GH-dependent mechanism. Reduced ATP generation in hypertrophied hearts of older Acro was associated with increased lactic acid levels suggesting that part of energy was due to glycolysis. Variations in ANT-1 expression were linked to GH through changes in NF-κB, the levels of which changed accordingly. In conclusion, 1-month-old acromegalic mice had increased ANT-1 expression and higher degree of ATP production. Long-standing disease was associated with a consistent reduction of ANT-1 and ATP tissue levels, which became GH-independent in older animals. This study demonstrated a direct effect of GH on key proteins involved in energy metabolism of acromegalic hearts.

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.

Protective role of adenine nucleotide translocase in O2-deficient hearts

1984 ◽  
Vol 247 (1) ◽  
pp. H25-H34
Author(s):  
S. V. Pande ◽  
T. Goswami ◽  
R. Parvin
Keyword(s):  
Fatty Acids ◽  
Adenine Nucleotide ◽  
Protective Role ◽  
Fatty Acyl ◽  
Adenine Nucleotide Translocase ◽  
Irreversible Damage ◽  
Rat Heart Mitochondria ◽  
A Site ◽  
Binding To Mitochondria

At subsaturating concentrations of palmitoyl-CoA, the carnitine-dependent oxidation of the palmitoyl portion by uncoupled rat heart mitochondria was stimulated by ADP or ATP. This effect was traced to the prevention of acyl-CoA binding to adenine nucleotide translocase and the consequent sparing of acyl-CoA for acylcarnitine formation. Palmitoyl-CoA oxidation was stimulated by ITP also although ITP served neither as a transportable substrate nor as an inhibitor of ADP transport. ITP and other nontransportable nucleoside di(tri)phosphates prevented octanoyl-CoA binding to mitochondria. ITP was bound to mitochondria, and this binding was reversed by ADP, octanoyl-CoA, and carboxyatractyloside. Thus, besides a substrate site, there is a site on the translocase that binds nucleoside di(tri)phosphates, CoA and its esters, and atractylosides; inhibition of the translocase results, however, only from the binding of CoA esters of fatty acids and of atractylosides. We suggest that in O2-deficient hearts, when nucleotides decline and fatty acyl-CoA rises, the binding of the latter to the translocase becomes operational to slow fatty acylcarnitine production. By retarding the rise in amphipathic burden, this mechanism could protect heart against irreversible damage during brief periods of ischemia or hypoxia.

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 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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