Woyda-Ploszczyca Andrzej M
Department of Bioenergetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.
J Enzyme Inhib Med Chem. 2025 Dec;40(1):2520611. doi: 10.1080/14756366.2025.2520611. Epub 2025 Jul 17.
Rapid GDP metabolism in mitochondria isolated from wild-type yeast is postulated. The hallmark of exogenous GDP is convergence with the effect of exogenous ADP, typically inducing oxidative phosphorylation (OXPHOS). The GDP-provoked changes in the presence of ATP, i.e. increased respiratory rate accompanied by decreased inner mitochondrial membrane electrical potential, were curtailed by OXPHOS inhibitors, such as carboxyatractyloside, which apparently merged the GDP effect with OXPHOS. However, all performed tests indicated that the response of mitochondria to GDP is indirect and involves two steps. First, GDP is transphosphorylated nucleoside diphosphate kinase (NDPK), ATP + GDP → ADP + GTP, which is followed by ADP-induced OXPHOS. Importantly, in mitochondria isolated from mutant yeast with a deleted NDPK gene, the stimulatory effect of GDP was eliminated. Therefore, a prerequisite for GDP metabolic action is the cooperation of NDPK with the OXPHOS apparatus. This biological model can help elucidate the molecular basis of some diseases treatment, such as cancer.
据推测，从野生型酵母中分离出的线粒体中存在快速的GDP代谢。外源性GDP的标志是与外源性ADP的作用趋同，通常会诱导氧化磷酸化（OXPHOS）。在ATP存在的情况下，GDP引起的变化，即呼吸速率增加，同时线粒体内膜电位降低，被OXPHOS抑制剂（如羧基苍术苷）所抑制，这显然将GDP的作用与OXPHOS合并。然而，所有进行的测试表明，线粒体对GDP的反应是间接的，涉及两个步骤。首先，GDP被核苷二磷酸激酶（NDPK）转磷酸化，ATP + GDP → ADP + GTP，随后是ADP诱导的OXPHOS。重要的是，在从具有缺失NDPK基因的突变酵母中分离出的线粒体中，GDP的刺激作用被消除。因此，GDP代谢作用的一个先决条件是NDPK与OXPHOS装置的合作。这种生物学模型有助于阐明某些疾病（如癌症）治疗的分子基础。
