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Woyda-Ploszczyca 2017 IOC124

From Bioblast
GDP-induced oxidative phosphorylation alleviates the GDP-dependent inhibitory effect on mitochondrial proton leak.

Link: Mitochondr Physiol Network 22.07

Woyda-Ploszczyca AM, Jarmuszkiewicz W (2017)

Event: IOC124

The purine nucleotide GDP is commonly used as a diagnostic inhibitor of mitochondrial uncoupling proteins (UCPs). UCPs belong to the mitochondrial carrier family and play the role of main catalysts of futile proton leak of the proton electrochemical gradient generated by the respiratory chain. However, we found that a high concentration of GDP (1 mM), but not GTP, stimulates respiratory rate and decreases membrane potential of mammalian (rat kidney and human endothelial cells) [1], plant (potato tubers), as well as unicellular eukaryote (amoeba) isolated mitochondria [2]. Therefore, we have observed exactly an opposite effect than that expected for the UCP-mediated H+ leak inhibition where an oxygen consumption rate inhibition is accompanied by an increase in mitochondrial membrane potential. We obtained the GDP stimulatory effect both in the absence and presence of exogenous free fatty acids (linoleic acid) considered strong positive effectors of UCP homologues. Interestingly, under conditions excluding oxidative phosphorylation, i.e. in the presence of carboxyatractyloside and/or oligomycin, the GDP stimulatory effect was completely abolished. We propose that the GDP-induced stimulatory effect depends on nucleoside diphosphate kinase (NDPK) activity. This enzyme transphosphorylates GDP in the presence of ATP and generates ADP pool (ATP + GDP β†’ ADP + GTP) what subsequently induces oxidative phosphorylation. Our results indicate that the GDP-dependent inhibition of UCPs could have a minor physiological significance and consequently GDP should not be used as a diagnostic inhibitor of UCPs.


β€’ Bioblast editor: Beno M, Kandolf G


Labels: MiParea: Comparative MiP;environmental MiP 


Organism: Human, Rat, Protists  Tissue;cell: Kidney, Endothelial;epithelial;mesothelial cell  Preparation: Isolated mitochondria 





References and support

  1. Woyda-Ploszczyca AM, Jarmuszkiewicz W (2014) Different effects of guanine nucleotides (GDP and GTP) on protein-mediated mitochondrial proton leak. PLoS One 9 e98969.
  2. Woyda-Ploszczyca AM, Jarmuszkiewicz W (2017) The conserved regulation of mitochondrial uncoupling proteins: From unicellular eukaryotes to mammals. BBA Bioenergetics 1858 21-33.
This work was supported by grants from the National Science Centre, Poland (2015/19/D/NZ3/00087 and 2016/21/B/NZ3/00333).

Affiliations

Adam Mickiewicz Univ Poznan, Fac Biol, Dept Bioenergetics, Poland. - [email protected]