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Insights into the functional aspects of Poly(ADP‐ribose) polymerase‐1 (PARP‐1) in mitochondrial homeostasis in Dictyostelium discoideum
Biology of the Cell ( IF 2.4 ) Pub Date : 2020-05-07 , DOI: 10.1111/boc.201900104
Ashlesha Kadam 1 , Tina Jubin 1 , Rittwika Roychowdhury 1 , Abhishek Garg 1 , Nishant Parmar 1 , Sayantani Pramanik Palit 1 , Rasheedunnisa Begum 1
Affiliation  

OBJECTIVE Poly(ADP-ribose) Polymerase-1 (PARP-1) is predominantly a nuclear protein and involved in various cellular processes like DNA repair, cell death, development, chromatin modulation etc. PARP-1 utilizes NAD+ and adds negatively charged PAR moieties on the target proteins. Overactivation of PARP-1 has been shown to cause energy crisis mediated cell death in which mitochondrial homeostasis is also affected. Moreover, the presence of mitochondrial NAD+ pools highlights the role of PARP-1 in mitochondria. The aim of present study is to understand the physiological role of PARP-1 in regulating mitochondrial functioning by varying the levels of PARP-1 in Dictyostelium discoideum. MATERIALS AND METHODS Intra-mitochondrial PARylation was analyzed by indirect immunofluorescence. Further, the effect of altered levels of PARP-1 i.e. overexpression, downregulation, knockout and its chemical inhibition was studied on mitochondrial respiration, ROS levels, ATP production, mitochondrial fission-fusion, mitochondrial morphology and mtDNA content of D. discoideum. RESULTS Our results show intra-mitochondrial PARylation under oxidative stress. Altered levels of PARP-1 caused impairment in the mitochondrial respiratory capacity, leading to elevated ROS levels and reduced ATP production. Moreover, PARP-1 affects the mitochondrial morphology and mtDNA content, alters the mitochondrial fission-fusion processes in lieu of preventing cell death under physiological conditions. CONCLUSION The current study highlights the physiological role of PARP-1 in mitochondrial respiration, its morphology, fission-fusion processes and mtDNA maintenance in D. discoideum. This article is protected by copyright. All rights reserved.

中文翻译:

聚(ADP-核糖)聚合酶-1(PARP-1)在盘基网柄菌线粒体稳态中的功能方面的见解

目的 Poly(ADP-ribose) Polymerase-1 (PARP-1) 主要是一种核蛋白,参与各种细胞过程,如 DNA 修复、细胞死亡、发育、染色质调节等。 PARP-1 利用 NAD+ 并添加带负电荷的 PAR 部分在目标蛋白质上。PARP-1 的过度激活已被证明会导致能量危机介导的细胞死亡,其中线粒体稳态也受到影响。此外,线粒体 NAD+ 池的存在突出了 PARP-1 在线粒体中的作用。本研究的目的是通过改变盘基网柄菌中 PARP-1 的水平来了解 PARP-1 在调节线粒体功能中的生理作用。材料和方法通过间接免疫荧光分析线粒体内PARylation。此外,改变 PARP-1 水平的影响,即过度表达,在线粒体呼吸、ROS 水平、ATP 产生、线粒体裂变融合、线粒体形态和 D. discoideum 的 mtDNA 含量方面研究了下调、敲除及其化学抑制。结果我们的结果显示氧化应激下的线粒体内PARylation。PARP-1 水平的改变导致线粒体呼吸能力受损,导致 ROS 水平升高和 ATP 产生减少。此外,PARP-1 影响线粒体形态和 mtDNA 含量,改变线粒体裂变融合过程,而不是在生理条件下防止细胞死亡。结论 目前的研究强调了 PARP-1 在 D. discoideum 线粒体呼吸、其形态、裂变融合过程和 mtDNA 维持中的生理作用。本文受版权保护。
更新日期:2020-05-07
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