The SFT-1 and OXA-1 respiratory chain complex assembly factors influence lifespan by distinct mechanisms in C. elegans

Longevity & Healthspan

Alison Woollard²  Garry Brown²  Carol Delaney¹  Ruth Brown²  Peter J Appleford²  Charles Brabin²  Joanne Harding³  Sara Maxwell² 

[1] Present address: Cytogenetics Department, South East Scotland Genetics Service, Western General Hospital, Edinburgh, UK;Biochemistry Department, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK;Present address: CRUK London Research Institute, 44 Lincoln’s Inn Fields, London, WC2A 3LY, UK

关键词: OXA-1;    SURF1;    C. elegans;    Lifespan;    Aging;    Respiratory chain complex;    Mitochondria;   

Others  :  803815
DOI  :  10.1186/2046-2395-2-9

 received in 2012-06-11, accepted in 2013-03-25,  发布年份 2013

【 摘 要 】

Background

C. elegans mitochondrial (Mit) mutants have disrupted mitochondrial electron transport chain function, yet, surprisingly, they are often long-lived, a property that has offered unique insights into the molecular mechanisms of aging. In this study, we examine the phenotypic consequences of reducing the expression of the respiratory chain complex assembly factors sft-1 (homologous to human SURF1) and oxa-1 (homologous to human OXA1) by RNA interference (RNAi). Mutations in human SURF1 are associated with Leigh syndrome, a neurodegenerative condition of the brain caused by cytochrome oxidase (COX) deficiency. Both SURF1 and OXA1 are integral proteins of the inner mitochondrial membrane, functioning in the COX assembly pathway.

Results

RNAi of both of these genes in C. elegans is associated with increased longevity, but the mechanism by which lifespan is extended is different in each case. sft-1(RNAi) animals display lifespan extension that is dependent on the daf-16 insulin-like signaling pathway, and associated with sensitivity to oxidative stress. oxa-1(RNAi) animals, in contrast, exhibit increased longevity that is at least partially independent of daf-16, and associated with a reduced developmental rate and increased resistance to oxidative stress.

Conclusions

This study further delineates the consequences of mitochondrial dysfunction within a whole organism that will ultimately help provide new models for human mitochondrial-associated diseases. The difference in phenotype observed upon down-regulation of these two COX assembly factors, as well as phenotypic differences between these factors and other respiratory chain components analyzed thus far, illustrates the complex inter-relationships that exist among energy metabolism, reproduction and aging even in this simplest of metazoan model organisms.

【 授权许可】

   
2013 Maxwell et al.; licensee BioMed Central Ltd.

【 图 表 】

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