Genetic dissection of cyclic pyranopterin monophosphate biosynthesis in plant mitochondria

被引:10
|
作者
Kruse, Inga [1 ,2 ]
Maclean, Andrew E. [1 ,2 ]
Hill, Lionel [1 ]
Balk, Janneke [1 ,2 ]
机构
[1] John Innes Ctr, Norwich NR4 7UH, Norfolk, England
[2] Univ East Anglia, Norwich NR4 7TJ, Norfolk, England
基金
英国生物技术与生命科学研究理事会;
关键词
MOLYBDENUM COFACTOR BIOSYNTHESIS; IRON-SULFUR PROTEINS; ARABIDOPSIS-THALIANA; HUMAN-DISEASE; ENZYME MOAA; BIOGENESIS; DEFICIENCY; BINDING; CLUSTER; MUTANT;
D O I
10.1042/BCJ20170559
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondria play a key role in the biosynthesis of two metal cofactors, iron-sulfur (FeS) clusters and molybdenum cofactor (Moco). The two pathways intersect at several points, but a scarcity of mutants has hindered studies to better understand these links. We screened a collection of sirtinol-resistant Arabidopsis thaliana mutants for lines with decreased activities of cytosolic FeS enzymes and Moco enzymes. We identified a new mutant allele of ATM3 (ABC transporter of the mitochondria 3), encoding the ATP-binding cassette transporter of the mitochondria 3 (systematic name ABCB25), confirming the previously reported role of ATM3 in both FeS cluster and Moco biosynthesis. We also identified a mutant allele in CNX2, cofactor of nitrate reductase and xanthine dehydrogenase 2, encoding GTP 3',8-cyclase, the first step in Moco biosynthesis which is localized in the mitochondria. A single-nucleotide polymorphism in cnx2-2 leads to substitution of Arg88 with Gln in the N-terminal FeS cluster-binding motif. cnx2-2 plants are small and chlorotic, with severely decreased Moco enzyme activities, but they performed better than a cnx2-1 knockout mutant, which could only survive with ammonia as a nitrogen source. Measurement of cyclic pyranopterin monophosphate (cPMP) levels by LC-MS/MS showed that this Moco intermediate was below the limit of detection in both cnx2-1 and cnx2-2, and accumulated more than 10-fold in seedlings mutated in the downstream gene CNX5. Interestingly, atm3-1 mutants had less cPMP than wild type, correlating with previous reports of a similar decrease in nitrate reductase activity. Taken together, our data functionally characterize CNX2 and suggest that ATM3 is indirectly required for cPMP synthesis.
引用
收藏
页码:495 / 509
页数:15
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