Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?
Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?
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DOI：
10.3389/fendo.2018.00196
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发表时间：
2018
影响因子：
5.2
通讯作者：
Kleinridders A
中科院分区：
文献类型：
--
作者：
Castro JP;Wardelmann K;Grune T;Kleinridders A
大脑通过中枢神经系统中神经元和神经胶质细胞的协同作用协调器官功能并调节全身代谢。为此，大脑具有非常高的能量消耗，并且主要依赖于葡萄糖利用和线粒体功能来发挥其功能。作为高速率代谢的结果，大脑中的线粒体随着时间的推移积累错误，例如线粒体DNA（mtDNA）突变、活性氧以及错误折叠和聚集的蛋白质。因此，线粒体需要采用特定的机制来避免或改善导致异常线粒体功能和氧化应激的受损蛋白质的增加。为了维持线粒体稳态（有丝分裂），细胞进化出穿梭、重折叠或与蛋白水解系统协调的分子伴侣，有助于维持错误折叠/聚集蛋白的低稳态水平。它们的重要性通过表现出伴侣作用降低的各种脑部疾病的发生来例证。在衰老、代谢疾病如2型糖尿病和神经退行性疾病如阿尔茨海默病（AD）、帕金森病（PD）或甚至亨廷顿病（HD）中已经观察到伴侣蛋白的损失（表达和/或功能），其中损伤蛋白的积累是有证据的。从这个角度来看，我们提出，适当的脑功能是通过线粒体伴侣的联合作用来维持的，以确保和维持有助于脑健康的有丝分裂，并且在失败时，改变脑功能，从而导致代谢疾病。
The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurodegenerative diseases such as Alzheimer’s (AD), Parkinson’s (PD) or even Huntington’s (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.
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影响因子：
3.5
作者：
Chatzispyrou IA;Alders M;Guerrero-Castillo S;Zapata Perez R;Haagmans MA;Mouchiroud L;Koster J;Ofman R;Baas F;Waterham HR;Spelbrink JN;Auwerx J;Mannens MM;Houtkooper RH;Plomp AS
通讯作者：
Plomp AS
影响因子：
9
作者：
通讯作者：
--
DOI：
10.1016/j.bbamcr.2015.06.016
发表时间：
2015-10-01
影响因子：
5.1
作者：
Al-Furoukh, Natalie;Ianni, Alessandro;Braun, Thomas
通讯作者：
Braun, Thomas
影响因子：
4.8
作者：
Boettinger, Lena;Oeljeklaus, Silke;Becker, Thomas
通讯作者：
Becker, Thomas
影响因子：
5.3
作者：
Cassina, Patricia;Cassina, Adriana;Radi, Rafael
通讯作者：
Radi, Rafael