Adenosine 5′-triphosphate: an intracellular metabolic messenger

Szewczyk, Adam; Pikula, Sławomir

doi:10.1016/s0005-2728(98)00094-2

Cited by 47 publications

(28 citation statements)

References 258 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that ATP increases the Ca 2+ -binding affinity of annexins in an isolated protein setup [55]. In fact, there is an entire class of annexins that shows this AdN-dependent Ca 2+ -binding (for reviews, see [56, 57]). This might explain some of our recent experimental data on the sudden rise in [Ca 2+ ] m during oxidative phosphorylation [58]; however, much more work remains to be done before any conclusion is reached.…”

Section: Resultsmentioning

confidence: 99%

Modeling the calcium sequestration system in isolated guinea pig cardiac mitochondria

Bazil

Blomeyer

Pradhan

et al. 2012

J Bioenerg Biomembr

View full text Add to dashboard Cite

Under high Ca 2+ load conditions, Ca 2+ concentrations in the extra-mitochondrial and mitochondrial compartments do not display reciprocal dynamics. This is due to a paradoxical increase in the mitochondrial Ca 2+ buffering power as the Ca 2+ load increases. Here we develop and characterize a mechanism of the mitochondrial Ca 2+ sequestration system using an experimental data set from isolated guinea pig cardiac mitochondria. The proposed mechanism elucidates this phenomenon and others in a mathematical framework and is integrated into a previously corroborated model of oxidative phosphorylation including the Na + /Ca 2+ cycle. The integrated model reproduces the Ca 2+ dynamics observed in both compartments of the isolated mitochondria respiring on pyruvate after a bolus of CaCl 2 followed by ruthenium red and a bolus of NaCl. The model reveals why changes in mitochondrial Ca 2+ concentration of Ca 2+ loaded mitochondria appear significantly mitigated relative to the corresponding extra-mitochondrial Ca 2+ concentration changes after Ca 2+ efflux is initiated. The integrated model was corroborated by simulating the set-point phenomenon. The computational results support the conclusion that the Ca 2+ sequestration system is composed of at least two classes of Ca 2+ buffers. The first class represents prototypical Ca 2+ buffering, and the second class encompasses the complex binding events associated with the formation of amorphous calcium phosphate. With the Ca 2+ sequestration system in mitochondria more precisely defined, computer simulations can aid in the development of innovative therapeutics aimed at addressing the myriad of complications that arise due to mitochondrial Ca 2+ overload.

show abstract

Section: Resultsmentioning

confidence: 99%

Modeling the calcium sequestration system in isolated guinea pig cardiac mitochondria

Bazil

Blomeyer

Pradhan

et al. 2012

J Bioenerg Biomembr

View full text Add to dashboard Cite

show abstract

“…Alternatively, it is also conceivable that there are differences in the time course for the activation of ATP-consuming events at the plasma membrane (fusion of secretory vesicles or ion pumping), compared with those within the cytosol. Intriguingly, control of [ATP] pm in the ␤-cell would appear to be distinct from that in heart cells, where ATP derived from glycolysis appears preferentially to inhibit K ATP channels (79,80 (84). With regard to the ␤-cell, perhaps the simplest model to explain our own observations is that an initial, small (Ca 2ϩ -independent) increase in [ATP] m , and subsequently in [ATP] pm , may begin to close K ATP channels, causing Ca 2ϩ influx.…”

Section: Response Of Primary Islet ␤-Cells To Increases In Extracellumentioning

confidence: 99%

Glucose Generates Sub-plasma Membrane ATP Microdomains in Single Islet β-Cells

Kennedy

Pouli

Ainscow

et al. 1999

Journal of Biological Chemistry

301

295

View full text Add to dashboard Cite

Increases in the concentration of free ATP within the islet ␤-cell may couple elevations in blood glucose to insulin release by closing ATP-sensitive K ؉ (K ATP ) channels and activating Ca 2؉ influx. Here, we use recombinant targeted luciferases and photon counting imaging to monitor changes in free [ATP] Increases in extracellular glucose concentration stimulate the exocytosis of insulin from islet ␤-cells. This is probably achieved by an increase in glycolysis and flux through the citrate cycle (1), leading to elevated intracellular levels of likely coupling factors (2), including ATP. Closure of ATP-sensitive K ϩ channels (3-5) then leads to plasma membrane depolarization and the influx of Ca 2ϩ through voltage gated Ca 2ϩ channels. Increases in the total intracellular concentration of ATP have been measured in isolated islets (6) and cell lines (7) exposed to increases in extracellular glucose concentration. However, the measured changes are generally small and difficult to interpret because of the large depot of intragranular ATP, and the presence of non-␤-cells (8). Furthermore, such measurements give no indication of the concentration of unbound ATP. Unfortunately, measurements of free [ATP] in living cells, for example by 31 P NMR (9), cannot easily be extended to the islet micro-organ and do not provide sufficient sensitivity to detect changes at the cellular or subcellular level. This is an important question because differences in [ATP] at different intracellular sites have been predicted. In particular, locally high ATP consumption by the plasma membrane Na ϩ -K ϩ and Ca 2ϩ -ATPase, may mean that [ATP] is lower in this domain than in the bulk of the cell cytosol (1). Similarly, the electrogenic nature of the mitochondrial ATP/ADP translocase (10) is predicted to create differences in ATP/ADP ratio across the inner mitochondrial membrane (cytosolic high).The role of changes in free Ca 2ϩ ion concentration ([Ca 2ϩ ]) in regulating ␤-cell metabolism and ATP concentration is controversial. Increases in [Ca 2ϩ ] following plasma membrane depolarization act both to stimulate ATP requiring processes (i.e. secretory granule movement and exocytosis) (11) and possibly to enhance mitochondrial oxidative metabolism (12, 13). Recent measurements of total ATP content of whole islets have suggested that the former may dominate and that Ca 2ϩ influx may diminish glucose-induced increases in ATP/ADP ratio (14).The use of firefly luciferase, targeted to discrete intracellular domains, should provide an extremely sensitive method of monitoring free [ATP] dynamically and at the subcellular level. In previous studies, we have shown that photon counting imaging of total luciferase activity in single cells provides a convenient means to measure changes in gene expression in single cells (15,16). Luciferase has previously been employed to measure intracellular ATP concentration in single cardiac myocytes (17) and hepatocytes (18), but only after microinjection of the purified protein. In recent reports, Maechler...

show abstract

“…(59,60) However, the role of GTP is becoming more apparent as it is involved in intracellular signaling through G proteins. (61) NTPases are enzymes that are able to interconvert different forms of energy.…”

Section: Annexins: a New And Distinct Class Of Ntpasesmentioning

confidence: 99%

Annexins as nucleotide‐binding proteins: Facts and speculations

2001

View full text Add to dashboard Cite

Annexins are ubiquitous multifunctional Ca2+ and phospholipid-binding proteins whose mechanism of function remains largely unknown. The accumulated in vitro experimental evidence indicates that ATP and GTP are functional ligands for nucleotide-sensitive annexin isoforms. Such nucleotide binding could modulate Ca2+ homeostasis, vesicular transport and/or signal transduction pathways and link them to cellular energy metabolism. Alternatively, since annexins are able to interact with other nucleotide-utilizing proteins, such as various kinases, GTPases and structural proteins, these proteins could influence the guanine nucleotide exchange metabolism and/or control the activity of various G proteins. The nucleotide-binding properties of annexins may affect the development or maintenance of some pathologies and diseases in which changes in physiological concentrations of purine nucleotides or disruption of Ca2+ homeostasis are crucial targets.

show abstract

Adenosine 5′-triphosphate: an intracellular metabolic messenger

Cited by 47 publications

References 258 publications

Modeling the calcium sequestration system in isolated guinea pig cardiac mitochondria

Modeling the calcium sequestration system in isolated guinea pig cardiac mitochondria

Glucose Generates Sub-plasma Membrane ATP Microdomains in Single Islet β-Cells

Annexins as nucleotide‐binding proteins: Facts and speculations

Contact Info

Product

Resources

About