RNAi of mitochondrial sirtuin, sir-2.2 reduces alpha-synuclein clearance and impairs energy homeostasis in C. elegans.

IF 3.3 3区 医学 Q2 CELL BIOLOGY
Anam Naseer, Pranoy Toppo, Mahmood Akbar, Aamir Nazir
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引用次数: 0

Abstract

Mitochondria are the regulators of energy production and play a vital role in modulating ageing and age-associated diseases. We investigated the role of sirtuins, a well-studied class of longevity-associated proteins (NAD+-dependent histone deacetylases), in mitochondrial biology and Parkinson's disease pathology. In particular, we endeavored to study the functional implications of mitochondrial sirtuin, sir-2.2 (ortholog of human SIRT4), in regulating neuroprotection employing Caenorhabditis elegans model. We observed that upon sir-2.2 knockdown, the alpha-synuclein aggregation was increased and expression of dopamine transporter, dat-1, was reduced. Also, the levels of marker proteins for innate immunity, oxidative stress, mitophagy, UPRmt, and autophagy, were decreased, suggesting an important function of sir-2.2 in maintaining mitochondrial homeostasis, regulating protein clearance and ameliorating the disease condition. Because of their crucial role in regulating oxidative stress and mitochondrial quality control, studying mitochondrial sirtuin will provide therapeutic insights into the metabolic regulation of ageing and neurodegeneration.

线粒体sirtuin, sir-2.2的RNAi降低了α -突触核蛋白的清除并损害了秀丽隐杆线虫的能量稳态。
线粒体是能量产生的调节器,在调节衰老和与年龄相关的疾病中起着至关重要的作用。我们研究了sirtuins在线粒体生物学和帕金森病病理中的作用,sirtuins是一类研究得很好的长寿相关蛋白(NAD+依赖性组蛋白去乙酰化酶)。特别是,我们利用秀丽隐杆线虫模型,努力研究线粒体sirtuin, sir-2.2(人类SIRT4的同源物)在调节神经保护中的功能意义。我们观察到,在sir-2.2敲除后,α -突触核蛋白聚集增加,多巴胺转运蛋白dat-1的表达减少。此外,先天免疫、氧化应激、线粒体自噬、UPRmt和自噬的标记蛋白水平下降,表明sir-2.2在维持线粒体稳态、调节蛋白质清除和改善疾病状况方面具有重要功能。由于它们在调节氧化应激和线粒体质量控制中的关键作用,研究线粒体sirtuin将为衰老和神经变性的代谢调节提供治疗性见解。
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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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