Zala Diana, Schlattner Uwe, Desvignes Thomas, Bobe Julien, Roux Aurélien, Chavrier Philippe, Boissan Mathieu
ESPCI - Paris, PSL Research University, Paris, F-75005, France.
CNRS, UMR8249, Paris, F-75005, France.
F1000Res. 2017 May 18;6:724. doi: 10.12688/f1000research.11561.2. eCollection 2017.
Nucleoside triphosphate (NTP)s, like ATP (adenosine 5'-triphosphate) and GTP (guanosine 5'-triphosphate), have long been considered sufficiently concentrated and diffusible to fuel all cellular ATPases (adenosine triphosphatases) and GTPases (guanosine triphosphatases) in an energetically healthy cell without becoming limiting for function. However, increasing evidence for the importance of local ATP and GTP pools, synthesised in close proximity to ATP- or GTP-consuming reactions, has fundamentally challenged our view of energy metabolism. It has become evident that cellular energy metabolism occurs in many specialised 'microcompartments', where energy in the form of NTPs is transferred preferentially from NTP-generating modules directly to NTP-consuming modules. Such energy channeling occurs when diffusion through the cytosol is limited, where these modules are physically close and, in particular, if the NTP-consuming reaction has a very high turnover, . is very processive. Here, we summarise the evidence for these conclusions and describe new insights into the physiological importance and molecular mechanisms of energy channeling gained from recent studies. In particular, we describe the role of glycolytic enzymes for axonal vesicle transport and nucleoside diphosphate kinases for the functions of dynamins and dynamin-related GTPases.
核苷三磷酸（NTP），如ATP（腺苷5'-三磷酸）和GTP（鸟苷5'-三磷酸），长期以来一直被认为在能量代谢健康的细胞中浓度足够高且具有扩散性，足以供给所有细胞ATP酶（腺苷三磷酸酶）和GTP酶（鸟苷三磷酸酶），而不会成为功能限制因素。然而，越来越多的证据表明，在靠近消耗ATP或GTP的反应处合成的局部ATP和GTP池具有重要性，这从根本上挑战了我们对能量代谢的看法。显而易见的是，细胞能量代谢发生在许多专门的“微区室”中，在这些微区室中，NTP形式的能量优先从产生NTP的模块直接转移到消耗NTP的模块。当通过细胞质的扩散受到限制时，就会发生这种能量通道化，此时这些模块在物理上很接近，特别是如果消耗NTP的反应具有非常高的周转率，并且是非常持续的。在这里，我们总结了支持这些结论的证据，并描述了从最近的研究中获得的关于能量通道化的生理重要性和分子机制的新见解。特别是，我们描述了糖酵解酶在轴突囊泡运输中的作用以及核苷二磷酸激酶在发动蛋白和发动蛋白相关GTP酶功能中的作用。
