Reduction of mitoferrin results in abnormal development and extended lifespan in Caenorhabditis elegans

Iron is essential for organisms. It is mainly utilized in mitochondria for biosynthesis of iron-sulfur clusters, hemes and other cofactors. Mitoferrin 1 and mitoferrin 2, two homologues proteins belonging to the mitochondrial solute carrier family, are required for iron delivery into mitochondria. Mitoferrin 1 is highly expressed in developing erythrocytes which consume a large amount of iron during hemoglobinization. Mitoferrin 2 is ubiquitously expressed, whose functions are less known. Zebrafish with mitoferrin 1 mutation show profound hypochromic anaemia and erythroid maturation arrests, and yeast with defects in MRS3/4, the counterparts of mitoferrin 1/2, has low mitochondrial iron levels and grows poorly by iron depletion. Mitoferrin 1 expression is up-regulated in yeast and mouse models of Fiedreich's ataxia disease and in human cell culture models of Parkinson disease, suggesting its involvement in the pathogenesis of diseases with mitochondrial iron accumulation. In this study we found that reduced mitoferrin levels in C. elegans by RNAi treatment causes pleiotropic phenotypes such as small body size, reduced fecundity, slow movement and increased sensitivity to paraquat. Despite these abnormities, lifespan was increased by 50% to 80% in N2 wild type strain, and in further studies using the RNAi sensitive strain eri-1, more than doubled lifespan was observed. The pathways or mechanisms responsible for the lifespan extension and other phenotypes of mitoferrin RNAi worms are worth further study, which may contribute to our understanding of aging mechanisms and the pathogenesis of iron disorder related diseases.

Ren, Yaguang
Yang, Su
Tan, Guoqiang
Ye, Wei
Liu, Danhui
Qian, Xu
Ding, Zhongying
Zhong, Yuhong
Zhang, Jingrui
Jiang, Dandan
Zhao, Yuhong
Lu, Jianxin
Item Type: 
Journal Article
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PloS One
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NCBI Published Medical (?)
PMID: 22253756 PMCID: PMC3256167

Turabian/Chicago Citation

Yaguang Ren, Su Yang, Guoqiang Tan, Wei Ye, Danhui Liu, Xu Qian, Zhongying Ding, Yuhong Zhong, Jingrui Zhang, Dandan Jiang, Yuhong Zhao and Jianxin Lu. 2012. "Reduction of mitoferrin results in abnormal development and extended lifespan in Caenorhabditis elegans." PloS One 7: 1: e29666. 10.1371/journal.pone.0029666.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1371/journal.pone.0029666 | issn = 1932-6203 | volume = 7 | pages = e29666 | last = Ren | first = Yaguang | coauthors = Yang, Su, Tan, Guoqiang, Ye, Wei, Liu, Danhui, Qian, Xu, Ding, Zhongying, Zhong, Yuhong, Zhang, Jingrui, Jiang, Dandan, Zhao, Yuhong, Lu, Jianxin | title = Reduction of mitoferrin results in abnormal development and extended lifespan in Caenorhabditis elegans | journal = PloS One | date = 2012 | pmid = | pmc = }} </ref>