title: Reduction of mitoferrin results in abnormal development and extended lifespan in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Ren
authors.forename: Su
authors.initials: S
authors.lastname: Yang
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Tan
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.forename: Danhui
authors.initials: D
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Ding
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhong
authors.forename: Jingrui
authors.initials: J
authors.lastname: Zhang
authors.forename: Dandan
authors.initials: D
authors.lastname: Jiang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D049628:Body Size / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006066:Gonads / Q000002:abnormalities / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008136:Longevity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010269:Paraquat / Q000633:toxicity; D034622:RNA Interference / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; D027682:Cation Transport Proteins; D012333:RNA, Messenger; C572390:mfn-1 protein, C elegans; D010269:Paraquat