IND1, a Fe-S protein involved in respiratory complex I biogenesis. From Arabidopsis gametogenesis defects to patients with mitochondrial myopathies

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• Mateusz Wydro, Plant Biochemistry
• Friday 09 March 2012, 13:00-13:30
• Department of Plant Sciences, Large Lecture Theatre.

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Mitochondria of most eukaryotic species contain a large, multi-subunit protein complex (NADH:ubiquinone oxidoreductase or Complex I). It plays a central role in oxidative phosphorylation by coupling electron transfer from NADH to quinone with proton translocation. Biosynthesis of complex I requires synchronized expression of two genomes: (i) the nuclear genome, encoding most of the 45 subunits; (ii) the mitochondrial genome which encodes 7 – 9 mostly hydrophobic subunits. Although recent years have brought significant progress in elucidating the structure of complex I, little is known about the assembly of this complicated complex. IND1 , a P-loop NTPase, Fe-S containing protein, was originally identified in Arabidopsis thaliana, however its evolutionary conservation in organisms containing complex I suggests a fundamental role in complex I biogenesis. In agreement with its phylogenetic distribution, IND1 has been shown to be required for the effective assembly of complex I, in yeast Yarrowia lipolytica, in human cell lines and Arabidopsis. Recently, mutations in the human homologue NUBPL were shown to cause a complex I deficiency in a patient with a mitochondrial myopathy (muscle disease). However, the mode of IND1 function in complex I biogenesis has not yet been fully elucidated. As IND1 is capable of binding a transferable Fe-S, we first hypothesised that it could play a role in delivering Fe-S to one of eight cluster binding sites in the hydrophilic arm of complex I. This hypothesis was tested in vitro. During characterisation of IND1 A . thaliana homologue (INDH), we have observed unusual genetic and phenotypic features of the heterozygous knock-out mutant, strikingly similar to those observed in mutants in organellar aminoacyl-tRNA synthetases. This finding led us to revise out hypothesis of the function of IND1 and drew our focus to its role in mt-tRNA metabolism. I will present the recently obtained data and propose a new function of IND1 in complex I biogenesis.

This talk is part of the Plant Sciences Research Seminars series.

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