PDF(Pubmed)
Abstract：
Introduction: Inorganic polyphosphate (polyP) is an ancient polymer which is extremely well-conserved throughout evolution, and found in every studied organism. PolyP is composed of orthophosphates linked together by high-energy bonds, similar to those found in ATP. The metabolism and the functions of polyP in prokaryotes and simple eukaryotes are well understood. However, little is known about its physiological roles in mammalian cells, mostly due to its unknown metabolism and lack of systematic methods and effective models for the study of polyP in these organisms. Methods: Here, we present a comprehensive set of genetically modified cellular models to study mammalian polyP. Specifically, we focus our studies on mitochondrial polyP, as previous studies have shown the potent regulatory role of mammalian polyP in the organelle, including bioenergetics, via mechanisms that are not yet fully understood. Results: Using SH-SY5Y cells, our results show that the enzymatic depletion of mitochondrial polyP affects the expression of genes involved in the maintenance of mitochondrial physiology, as well as the structure of the organelle. Furthermore, this depletion has deleterious effects on mitochondrial respiration, an effect that is dependent on the length of polyP. Our results also show that the depletion of mammalian polyP in other subcellular locations induces significant changes in gene expression and bioenergetics; as well as that SH-SY5Y cells are not viable when the amount and/or the length of polyP are increased in mitochondria. Discussion: Our findings expand on the crucial role of polyP in mammalian mitochondrial physiology and place our cell lines as a valid model to increase our knowledge of both mammalian polyP and mitochondrial physiology.
摘要：
简介：无机多磷酸盐（polyP）是一种古老的聚合物，在整个进化过程中都非常保守。并在每个被研究的有机体中发现。PolyP由通过高能键连接在一起的正磷酸盐组成，类似于在ATP中发现的那些。polyP在原核生物和简单真核生物中的代谢和功能是众所周知的。然而,对它在哺乳动物细胞中的生理作用知之甚少，主要是由于其未知的代谢以及缺乏用于研究这些生物中polyP的系统方法和有效模型。方法:这里,我们提出了一套全面的转基因细胞模型来研究哺乳动物polyP。具体来说,我们的研究重点是线粒体polyP,正如以前的研究表明哺乳动物polyP在细胞器中的有效调节作用，包括生物能学，通过尚未完全理解的机制。结果:使用SH-SY5Y细胞,我们的结果表明，线粒体polyP的酶耗竭会影响线粒体生理维持基因的表达，以及细胞器的结构。此外，这种耗竭对线粒体呼吸有有害影响，这种影响取决于polyP的长度。我们的结果还表明，哺乳动物polyP在其他亚细胞位置的消耗会引起基因表达和生物能量学的显着变化；以及当线粒体中polyP的数量和/或长度增加时，SH-SY5Y细胞无法存活。讨论：我们的发现扩展了polyP在哺乳动物线粒体生理学中的关键作用，并将我们的细胞系作为有效的模型来增加我们对哺乳动物polyP和线粒体生理学的了解。
