Toolkit for cellular studies of mammalian mitochondrial inorganic polyphosphate.
Toolkit for cellular studies of mammalian mitochondrial inorganic polyphosphate.
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DOI：
10.3389/fcell.2023.1302585
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
简介： 无机多磷酸盐 (polyP) 是一种古老的聚合物，在整个进化过程中极其保守，在每个研究的生物体中都有发现。 PolyP 由通过高能键连接在一起的正磷酸盐组成，类似于 ATP 中的键。多聚磷在原核生物和简单真核生物中的代谢和功能已广为人知。然而，人们对其在哺乳动物细胞中的生理作用知之甚少，这主要是由于其代谢未知以及缺乏系统的方法和有效的模型来研究polyP在这些生物体中的作用。 方法：在这里，我们提出了一套全面的转基因细胞模型来研究哺乳动物多聚体。具体来说，我们的研究重点是线粒体多聚蛋白，因为之前的研究表明哺乳动物多聚蛋白通过尚未完全了解的机制在细胞器中发挥有效的调节作用，包括生物能学。 结果：使用 SH-SY5Y 细胞，我们的结果表明，线粒体 PolyP 的酶耗竭会影响参与维持线粒体生理学的基因的表达以及细胞器的结构。此外，这种消耗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，哺乳动物其他亚细胞位置中polyP的消耗会引起基因表达和生物能学的显着变化；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：我们的研究结果扩展了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模型来增加我们对哺乳动物polyP和线粒体生理学的了解。
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.
影响因子：
3.7
作者：
Vinciguerra, C.;Di Fonzo, A.;Monfrini, E.;Ronchi, D.;Cuoco, S.;Piscosquito, G.;Barone, P.;Pellecchia, M. T.
通讯作者：
Pellecchia, M. T.