Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner.

Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner.
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DOI:
10.1038/s41467-021-22001-w
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发表时间:
2021-03-19
影响因子:
16.6
通讯作者:
Hine C
Hine C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bithi N;Link C;Henderson YO;Kim S;Yang J;Li L;Wang R;Willard B;Hine C

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硫化氢(H_2S)是一种细胞保护的氧化还原活性代谢产物,通过蛋白过硫化(R-SSnH)传递信号。尽管已知过硫化的重要性,但组织特有的过硫化轮廓及其相关功能尚未得到很好的表征,特别是在已知调节硫化氢产生的条件和干预下。我们假设,饮食限制(DR)可以延长寿命并促进硫化氢的产生,从而扩大组织特异性的过硫脲。在这里,我们发现在两种形式的DR下,蛋白质过硫化在年轻和老年雄性小鼠的肝脏、肾脏、肌肉和脑中丰富,但在心脏中减少,DR在许多代谢和衰老相关的途径中促进过硫化。缺乏胱硫醚γ裂解酶(Cgl)的小鼠对DR的反应总体上减少了组织蛋白的过硫化数量,并未能从功能上增强过硫脲,主要是在肾脏、肌肉和脑中。在这里,我们定义了组织和CGL依赖的过硫脲以及饮食如何改变它们的组成,强调了DR和H2S影响生物过程和有机体健康的广度。饮食限制(DR)可以增加蛋白质过硫化,但这一过程的组织特异性还不是很清楚。在这里,作者比较了年轻和老年小鼠在DR下的器官特异性蛋白过硫体,并表明DR依赖的过硫体的变化依赖于胱硫醚γ裂解酶。
Hydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSnH). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions and interventions known to modulate H2S production. We hypothesize that dietary restriction (DR), which increases lifespan and can boost H2S production, expands tissue-specific persulfidomes. Here, we find protein persulfidation enriched in liver, kidney, muscle, and brain but decreased in heart of young and aged male mice under two forms of DR, with DR promoting persulfidation in numerous metabolic and aging-related pathways. Mice lacking cystathionine γ-lyase (CGL) have overall decreased tissue protein persulfidation numbers and fail to functionally augment persulfidomes in response to DR, predominantly in kidney, muscle, and brain. Here, we define tissue- and CGL-dependent persulfidomes and how diet transforms their makeup, underscoring the breadth for DR and H2S to impact biological processes and organismal health. Dietary restriction (DR) can increase protein persulfidation but the tissue specificity of this process is not well understood. Here, the authors compare organ-specific protein persulfidomes in young and aged mice under DR, and show that DR-dependent persulfidome changes depend on cystathionine γ-lyase.
DOI: 10.1016/j.cell.2015.02.020
发表时间: 2015-03-26
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