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Dietary iron loading negatively affects liver mitochondrial function
Metallomics ( IF 2.9 ) Pub Date : 2017-10-06 00:00:00 , DOI: 10.1039/c7mt00177k Chiara Volani 1, 2, 3, 4, 5 , Carolina Doerrier 3, 6, 7 , Egon Demetz 1, 2, 3 , David Haschka 1, 2, 3 , Giuseppe Paglia 4, 5 , Alexandros A. Lavdas 4, 5 , Erich Gnaiger 3, 6, 7, 7, 8 , Guenter Weiss 1, 2, 3
Metallomics ( IF 2.9 ) Pub Date : 2017-10-06 00:00:00 , DOI: 10.1039/c7mt00177k Chiara Volani 1, 2, 3, 4, 5 , Carolina Doerrier 3, 6, 7 , Egon Demetz 1, 2, 3 , David Haschka 1, 2, 3 , Giuseppe Paglia 4, 5 , Alexandros A. Lavdas 4, 5 , Erich Gnaiger 3, 6, 7, 7, 8 , Guenter Weiss 1, 2, 3
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Iron is an essential co-factor for several metabolic processes, including mitochondrial respiration, and mitochondria are the major sites of iron-utilization. Cellular iron homeostasis must be tightly regulated, as intracellular iron deficiency can lead to insufficient energy production, whereas iron overload triggers ROS (reactive oxygen species) formation via the Fenton reaction. So far little is known on how iron imbalances affect mitochondrial function in vivo and the impact of the genotype on that, we studied the effects of dietary iron loading on mitochondrial respiratory capacity in liver by comparing two genetically divergent mouse strains, namely C57BL/6N and FVB mice. Both mouse strains differed in their basal iron levels and their metabolic responses to iron loading as determined by expression of iron trafficking proteins (ferritin was increased in livers of animals receiving high iron diet) as well as tissue iron content (2-fold increase, FVB p = 0.0013; C57BL/6N p = 0.0022). Dietary iron exposure caused a significant impairment of mitochondrial oxidative phosphorylation, especially regarding OXPHOS capacity (FVB p = 0.0006; C57BL/6N p = 0.0087) and S-ETS capacity (FVB p = 0.0281; C57BL/6N p = 0.0159). These effects were more pronounced in C57BL/6N than in FVB mice and were paralleled by an iron mediated induction of oxidative stress in mitochondria. The increased susceptibility of C57BL6/N mice to iron loading may be due to reduced expression of anti-oxidant defense mechanisms and altered iron trafficking upon dietary challenge pointing to a role of genetic modifiers for cellular and mitochondrial iron trafficking. Finally, iron-mediated induction of mitochondrial oxidative stress and reduction of oxidative phosphorylation may underlie fatigue in subjects with iron loading diseases.
中文翻译：
膳食铁负荷对肝线粒体功能产生负面影响
铁是包括线粒体呼吸在内的几种代谢过程的重要辅助因子，而线粒体是利用铁的主要场所。细胞内铁稳态必须严格控制，因为细胞内铁缺乏会导致能量产生不足，而铁超载则通过Fenton反应触发ROS（活性氧）的形成。迄今为止，关于铁的不平衡如何影响体内线粒体功能的知识还知之甚少以及该基因型的影响，我们通过比较两种遗传上不同的小鼠品系C57BL / 6N和FVB小鼠，研究了膳食铁负荷对肝脏线粒体呼吸能力的影响。两种小鼠品系的基础铁水平和对铁负荷的代谢反应均不同，这取决于铁运输蛋白的表达（在接受高铁饮食的动物的肝脏中铁蛋白增加）以及组织铁含量（2倍增加，FVB）p = 0.0013； C57BL / 6N p = 0.0022）。饮食中铁的暴露引起线粒体氧化磷酸化的严重损害，特别是关于OXPHOS容量（FVB p = 0.0006； C57BL / 6N p = 0.0087）和S-ETS容量（FVB）。p = 0.0281；C57BL / 6N p = 0.0159）。这些作用在C57BL / 6N中比在FVB小鼠中更为明显，并与线粒体中铁介导的氧化应激诱导相平行。C57BL6 / N小鼠对铁负荷的敏感性增加可能是由于抗氧化剂防御机制的表达降低以及饮食挑战后铁运输的改变，从而表明遗传修饰剂在细胞和线粒体铁运输中的作用。最后，铁介导的线粒体氧化应激的诱导和氧化磷酸化的减少可能是患有铁负荷疾病的受试者疲劳的基础。
更新日期：2017-11-16
中文翻译：
膳食铁负荷对肝线粒体功能产生负面影响
铁是包括线粒体呼吸在内的几种代谢过程的重要辅助因子，而线粒体是利用铁的主要场所。细胞内铁稳态必须严格控制，因为细胞内铁缺乏会导致能量产生不足，而铁超载则通过Fenton反应触发ROS（活性氧）的形成。迄今为止，关于铁的不平衡如何影响体内线粒体功能的知识还知之甚少以及该基因型的影响，我们通过比较两种遗传上不同的小鼠品系C57BL / 6N和FVB小鼠，研究了膳食铁负荷对肝脏线粒体呼吸能力的影响。两种小鼠品系的基础铁水平和对铁负荷的代谢反应均不同，这取决于铁运输蛋白的表达（在接受高铁饮食的动物的肝脏中铁蛋白增加）以及组织铁含量（2倍增加，FVB）p = 0.0013； C57BL / 6N p = 0.0022）。饮食中铁的暴露引起线粒体氧化磷酸化的严重损害，特别是关于OXPHOS容量（FVB p = 0.0006； C57BL / 6N p = 0.0087）和S-ETS容量（FVB）。p = 0.0281；C57BL / 6N p = 0.0159）。这些作用在C57BL / 6N中比在FVB小鼠中更为明显，并与线粒体中铁介导的氧化应激诱导相平行。C57BL6 / N小鼠对铁负荷的敏感性增加可能是由于抗氧化剂防御机制的表达降低以及饮食挑战后铁运输的改变，从而表明遗传修饰剂在细胞和线粒体铁运输中的作用。最后，铁介导的线粒体氧化应激的诱导和氧化磷酸化的减少可能是患有铁负荷疾病的受试者疲劳的基础。
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