期刊
BIOCHEMICAL JOURNAL
卷 441, 期 -, 页码 945-953出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20111574
关键词
frataxin; Friedreich's ataxia; malate-aspartate NADH shuttle; mitochondrion; protein acetylation; yeast
资金
- Association Francaise Ataxie de Friedreich (AFAF), France
- 'Agence Nationale de la Recherche' ('ANR Maladies Rares'), France [ANR-06-MRAR-025-01]
- AFAF
Friedreich's ataxia is a hereditary neurodegenerative disease caused by reduced expression of mitochondrial frataxin. Frataxin deficiency causes impairment in respiratory capacity, disruption of iron homoeostasis and hypersensitivity to oxidants. Although the redox properties of NAD (NAD(+) and NADH) are essential for energy metabolism, only few results are available concerning homoeostasis of these nucleotides in frataxin-deficient cells. In the present study, we show that the malate aspartate NADH shuttle is impaired in Saccharomyces cerevisiae frataxin-deficient cells (Delta yfh1) due to decreased activity of cytosolic and mitochondrial isoforms of malate dehydrogenase and to complete inactivation of the mitochondrial aspartate aminotransferase (Aat1). A considerable decrease in the amount of mitochondrial acetylated proteins was observed in the Delta yfh1 mutant compared with wild-type. Aat1 is acetylated in wild-type mitochondria and deacetylated in Delta yfh1 mitochondria suggesting that inactivation could be due to this post-translational modification. Mutants deficient in iron sulfur cluster assembly or lacking mitochondrial DNA also showed decreased activity of Aat1, suggesting that Aat1 inactivation was a secondary phenotype in Delta yfh1 cells. Interestingly, deletion of the AAT1 gene in a wild-type strain caused respiratory deficiency and disruption of iron homoeostasis without any sensitivity to oxidative stress. Our results show that secondary inactivation of Aat1 contributes to the amplification of the respiratory defect observed in Delta yfh1 cells. Further implication of mitochondrial protein deacetylation in the physiology of frataxin-deficient cells is anticipated.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据