Structural and functional characterization of FoF1-ATP synthase on the extracellular surface of rat hepatocytes

Mangiullo, Roberto; Gnoni, Antonio; Leone, Antonella; Gnoni, Gabriele V.; Papa, Sergio; Zanotti, Franco

doi:10.1016/j.bbabio.2008.08.003

Cited by 83 publications

(84 citation statements)

References 36 publications

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“…in the absence of a closed vesicle. 38,53 The proposed proteolipidic H þ translocation would help understand extramitochondrial ATP synthases, acting without any transmembrane H þ gradient. The hypothesis that myelin could act like a mitochondrion to contribute to the energetic metabolism of neurons has been criticized by Harris and Attwell.…”

Section: Discussionmentioning

confidence: 99%

“…Rather, it reveals the still unrecognized potential of Mitchell's theory, also in being extendable to the emerging awareness of extramitochondrial OXPHOS. 49 New roles emerge for ATP synthases, some of which were recently shown to be ectopically expressed in many cellular membranes where they would conduct extramitochondrial OXPHOS (HUVEC cells, 50 rod outer segments, 51,52 rat hepatocytes, 53 isolated myelin, 54 and cancer cells. 38 In particular, the present hypothesis is consistent with the reported possibility to conduct OXPHOS on a plasma membrane, i.e.…”

Section: Discussionmentioning

confidence: 99%

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Hypothesis of Lipid-Phase-Continuity Proton Transfer for Aerobic ATP Synthesis

Morelli

Ravera

Calzia

et al. 2013

J Cereb Blood Flow Metab

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The basic processes harvesting chemical energy for life are driven by proton (H þ ) movements. These are accomplished by the mitochondrial redox complex V, integral membrane supramolecular aggregates, whose structure has recently been described by advanced studies. These did not identify classical aqueous pores. It was proposed that H þ transfer for oxidative phosphorylation (OXPHOS) does not occur between aqueous sources and sinks, where an energy barrier would be insurmountable. This suggests a novel hypothesis for the proton transfer. A lipid-phase-continuity H þ transfer is proposed in which H þ are always bound to phospholipid heads and cardiolipin, according to Mitchell's hypothesis of asymmetric vectorial H þ diffusion. A phase separation is proposed among the proton flow, following an intramembrane pathway, and the ATP synthesis, occurring in the aqueous phase. This view reminiscent of Grotthus mechanism would better account for the distance among the F o and F 1 moieties of F o F 1 -ATP synthase, for its mechanical coupling, as well as the necessity of a lipid membrane. A unique active role for lipids in the evolution of life can be envisaged. Interestingly, this view would also be consistent with the evidence of an OXPHOS outside mitochondria also found in non-vesicular membranes, housing the redox complexes. Journal of Cerebral Blood INTRODUCTIONChemical energy for living matter is mostly supplied by the F o F 1 -ATP synthases (ATP synthases), multimeric proteins, which employ a rotary mechanism driven by proton-motive force. In turn, protons (H þ ) are translocated by electron transport chain (ETC). The structure and organization of ATP synthases, the 'splendid nanomolecular machine' 1 that mechanically synthesize ATP from ADP and Pi are well described, but how its rotation is driven by proton flow and how this energy is converted into catalysis are less clear.2 F 1 moiety is peculiar in that it is the only enzyme as yet known channeling energy to the reactant species by means of mechanical force. The topic of H þ cycling, pivotal in oxidative phosphorylation, is central in energy conversion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hypothesis of Lipid-Phase-Continuity Proton Transfer for Aerobic ATP Synthesis

Morelli

Ravera

Calzia

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that this protein, as part of the whole and active F1/F0 complex, is present on the surface of endothelial cells, tumor cells, [28][29][30] and multiple cell lines. [31][32][33][34] ATP synthase is a protein present on the inner membrane of the mitochondria. The mechanism by which it migrates to the surface of the cell is not understood.…”

Section: Discussionmentioning

confidence: 99%

Ectopic ATP synthase facilitates transfer of HIV-1 from antigen-presenting cells to CD4+ target cells

Yavlovich

Viard

Zhou

et al. 2012

Blood

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Antigen-presenting cells (APCs) act as vehicles that transfer HIV to their target CD4+ cells through an intercellular junction, termed the virologic synapse. The molecules that are involved in this process remain largely unidentified. In this study, we used photoaffinity labeling and a proteomic approach to identify new proteins that facilitate HIV-1 transfer. We identified ectopic mitochondrial ATP synthase as a factor that mediates HIV-1 transfer between APCs and CD4+ target cells. Monoclonal antibodies against the β-subunit of ATP synthase inhibited APC-mediated transfer of multiple strains HIV-1 to CD4+ target cells. Likewise, the specific inhibitors of ATPase, citreoviridin and IF1, completely blocked APC-mediated transfer of HIV-1 at the APC-target cell interaction step. Confocal fluorescent microscopy showed localization of extracellular ATP synthase at junctions between APC and CD4+ target cells. We conclude that ectopic ATP synthase could be an accessible molecular target for inhibiting HIV-1 proliferation in vivo.

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“…Ca 2+ -ATPase is located in hepatocyte plasma membranes and is involved in calcium homeostasis [57]. A functionally active ecto-F 0 F 1 -ATP synthase has been identified on the plasma membrane of hepatocytes that mediates extracellular formation from ADP and inorganic phosphate [173]. Membrane-bound ATP synthesis has a role in modulating the concentrations of extracellular ADP and is regulated by a plasma apoliproprotein [175].…”

Section: Inflammation Liver Injury and Immune Regulationmentioning

confidence: 99%

Purinergic signalling in the liver in health and disease

Burnstock

Vaughn

Robson

2013

Purinergic Signalling

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Purinergic signalling is involved in both the physiology and pathophysiology of the liver. Hepatocytes, Kupffer cells, vascular endothelial cells and smooth muscle cells, stellate cells and cholangiocytes all express purinoceptor subtypes activated by adenosine, adenosine 5′-triphosphate, adenosine diphosphate, uridine 5′-triphosphate or UDP. Purinoceptors mediate bile secretion, glycogen and lipid metabolism and indirectly release of insulin. Mechanical stress results in release of ATP from hepatocytes and Kupffer cells and ATP is also released as a cotransmitter with noradrenaline from sympathetic nerves supplying the liver. Ectonucleotidases play important roles in the signalling process. Changes in purinergic signalling occur in vascular injury, inflammation, insulin resistance, hepatic fibrosis, cirrhosis, diabetes, hepatitis, liver regeneration following injury or transplantation and cancer. Purinergic therapeutic strategies for the treatment of these pathologies are being explored.

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Structural and functional characterization of FoF1-ATP synthase on the extracellular surface of rat hepatocytes

Cited by 83 publications

References 36 publications

Hypothesis of Lipid-Phase-Continuity Proton Transfer for Aerobic ATP Synthesis

Hypothesis of Lipid-Phase-Continuity Proton Transfer for Aerobic ATP Synthesis

Ectopic ATP synthase facilitates transfer of HIV-1 from antigen-presenting cells to CD4+ target cells

Purinergic signalling in the liver in health and disease

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