Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study.
Mitochondrial Inorganic Polyphosphate (polyP) Is a Potent Regulator of Mammalian Bioenergetics in SH-SY5Y Cells: A Proteomics and Metabolomics Study.
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DOI：
10.3389/fcell.2022.833127
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发表时间：
2022
影响因子：
5.5
通讯作者：
Solesio ME
中科院分区：
文献类型：
--
作者：
Guitart-Mampel M;Urquiza P;Carnevale Neto F;Anderson JR;Hambardikar V;Scoma ER;Merrihew GE;Wang L;MacCoss MJ;Raftery D;Peffers MJ;Solesio ME
无机聚磷酸盐（polyP）是一种古老的、普遍存在的、保存良好的聚合物，存在于所有被研究的生物中。它是由正磷酸盐的单个亚基组成的，这些亚基通过结构相似的键连接在一起，与ATP中的键具有等能。虽然polyP的代谢和生理作用已经在一些生物体中得到了描述，包括细菌和酵母，但这种聚合物在哺乳动物生理学中的确切作用仍然知之甚少。在这些生物体中，息肉蛋白与线粒体共定位，其作为应激反应的关键调节因子，包括维持适当的生物能量学，已经被我们的团队和其他人证明。在这里，我们使用野生型（Wt）和MitoPPX（酶促线粒体息肉的细胞）SH-SY5Y细胞，利用蛋白质组学和代谢组学方法对细胞生理状态进行了全面的研究。我们的研究结果表明，与Wt细胞相比，MitoPPX细胞中线粒体生理学，特别是生物能量学的明显失调。此外，息肉酶耗竭引起的影响类似于在神经退行性疾病和神经元衰老中观察到的线粒体功能障碍。基于我们的研究结果，线粒体息肉的代谢可能是治疗这些疾病的有效和创新的药理学靶点。
Inorganic polyphosphate (polyP) is an ancient, ubiquitous, and well-conserved polymer which is present in all the studied organisms. It is formed by individual subunits of orthophosphate which are linked by structurally similar bonds and isoenergetic to those found in ATP. While the metabolism and the physiological roles of polyP have already been described in some organisms, including bacteria and yeast, the exact role of this polymer in mammalian physiology still remains poorly understood. In these organisms, polyP shows a co-localization with mitochondria, and its role as a key regulator of the stress responses, including the maintenance of appropriate bioenergetics, has already been demonstrated by our group and others. Here, using Wild-type (Wt) and MitoPPX (cells enzymatically depleted of mitochondrial polyP) SH-SY5Y cells, we have conducted a comprehensive study of the status of cellular physiology, using proteomics and metabolomics approaches. Our results suggest a clear dysregulation of mitochondrial physiology, especially of bioenergetics, in MitoPPX cells when compared with Wt cells. Moreover, the effects induced by the enzymatic depletion of polyP are similar to those present in the mitochondrial dysfunction that is observed in neurodegenerative disorders and in neuronal aging. Based on our findings, the metabolism of mitochondrial polyP could be a valid and innovative pharmacological target in these conditions.
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影响因子：
9
作者：
Chowdhury SR;Ray U;Chatterjee BP;Roy SS
通讯作者：
Roy SS
肌酸阻止了肌源性，氧化压力C2C12细胞的线粒体对线粒体的结构和功能损害，并恢复其分化能力。
影响因子：
--
作者：
Barbieri E;Guescini M;Calcabrini C;Vallorani L;Diaz AR;Fimognari C;Canonico B;Luchetti F;Papa S;Battistelli M;Falcieri E;Romanello V;Sandri M;Stocchi V;Ciacci C;Sestili P
通讯作者：
Sestili P
影响因子：
64.5
作者：
Fedorenko A;Lishko PV;Kirichok Y
通讯作者：
Kirichok Y
DOI：
10.1073/pnas.0708959104
发表时间：
2007-11-13
影响因子：
11.1
作者：
Abramov, Andrey Y.;Fraley, Cresson;Pavlov, Evgeny
通讯作者：
Pavlov, Evgeny
影响因子：
4.8
作者：
Castro, Cristina M.;Corciulo, Carmen;Cronstein, Bruce N.
通讯作者：
Cronstein, Bruce N.