Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic acid production

Wada, Hajime; Shintani, David K.; Ohlrogge, John B.

doi:10.1073/pnas.94.4.1591

Cited by 201 publications

(173 citation statements)

References 43 publications

(34 reference statements)

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“…In this study we prepared a polyclonal antibody specific to lipoic acid synthase of Arabidopsis and investigated its intracellular localization in Arabidopsis cells. The obtained results demonstrated that lipoic acid synthase is present in mitochondria, suggesting that the biosynthesis of lipoic acid takes place in mitochondria, which is consistent with the previous observation that a major part of de novo synthesized fatty acids in mitochondria may be used for biosynthesis of lipoic acid (Wada et al, 1997).…”

Section: Discussionsupporting

confidence: 80%

“…Octanoic acid has been shown to be the precursor of the carbon chain (White, 1980;Parry, 1983), but neither the origin nor the mechanism whereby the sulfur atoms are inserted into the carbon chain is known. We recently investigated the function of mitochondrial ACP, which was discovered in the mitochondria of several organisms (Shintani and Ohlrogge, 1994;Schneider et al, 1997), and found that it is involved in the biosynthesis of fatty acids in mitochondria of pea and Neurospora (Wada et al, 1997). We also found that octanoyl-ACP is synthesized in mitochondria as an intermediate of fatty acid synthesis and may be used for the biosynthesis of lipoic acid (Wada et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, these researchers cloned a cDNA for the bovine lipoyltransferase and found that both isoforms are derived from the same translated product but are processed differently (Fujiwara et al, 1997). We recently studied fatty acid synthesis in mitochondria isolated from pea and found that a major part of the de novo-synthesized fatty acids may be used for the biosynthesis of lipoic acid (Wada et al, 1997). Together these results have begun to define the biosynthesis of lipoic acid and its intracellular organization in eukaryotes.…”

mentioning

confidence: 96%

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Biosynthesis of Lipoic Acid in Arabidopsis: Cloning and Characterization of the cDNA for Lipoic Acid Synthase

Yasuno

Wada

1998

Plant Physiology

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Lipoic acid is a coenzyme that is essential for the activity of enzyme complexes such as those of pyruvate dehydrogenase and glycine decarboxylase. We report here the isolation and characterization of LIP1 cDNA for lipoic acid synthase of Arabidopsis. The Arabidopsis LIP1 cDNA was isolated using an expressed sequence tag homologous to the lipoic acid synthase of Escherichia coli. This cDNA was shown to code for Arabidopsis lipoic acid synthase by its ability to complement a lipA mutant of E. coli defective in lipoic acid synthase. DNA-sequence analysis of the LIP1 cDNA revealed an open reading frame predicting a protein of 374 amino acids. Comparisons of the deduced amino acid sequence with those of E. coli and yeast lipoic acid synthase homologs showed a high degree of sequence similarity and the presence of a leader sequence presumably required for import into the mitochondria. Southernhybridization analysis suggested that LIP1 is a single-copy gene in Arabidopsis. Western analysis with an antibody against lipoic acid synthase demonstrated that this enzyme is located in the mitochondrial compartment in Arabidopsis cells as a 43-kD polypeptide.Lipoic acid (6,8-thioctic acid) is a sulfur-containing coenzyme that is required for the activity of enzyme complexes involved in the oxidative decarboxylation of ␣-ketoacids (Reed and Hackert, 1990;Perham, 1991;Mattevi et al., 1992) and in the Gly-cleavage system (Fujiwara et al., 1990;Kim and Oliver, 1990;Macherel et al., 1990). There are five lipoyl proteins: the dihydrolipoamide acyltransferase subunits of pyruvate, ␣-ketoglutarate, branched-chain ␣-ketoacid dehydrogenase complexes, protein X of the pyruvate dehydrogenase complex, and the H-protein of the Gly-cleavage system. Lipoic acid is covalently bound to these proteins via an amide linkage to the ⑀-amino group of specific Lys residues (Reed and Hackert, 1966). The lipoylLys arm functions as a carrier of reaction intermediates, and reducing equivalents interact with the active sites of the components of the complexes (Yeaman, 1989; Douce et al., 1994).Despite the importance of the lipoyl-prosthetic group in the functioning of several enzyme complexes, the biosynthesis of lipoic acid is not well understood in any organism. Molecular genetic studies (Vanden Boom et al., 1991;Reed and Cronan, 1993;Morris et al., 1994Morris et al., , 1995 of Escherichia coli have identified three genes, lipA, lipB, and lplA that are involved in the biosynthesis and transfer of lipoic acid. lipA encodes a lipoic acid synthase that is required for an insertion of the first sulfur atom into the octanoate backbone (Reed and Cronan, 1993). lplA and lipB encode lipoate ligases that are involved in the transfer of lipoic acid to cognate proteins (Morris et al., 1994(Morris et al., , 1995. LplA and LipB proteins primarily function in the utilization of lipoic acid exogenously added to the growth medium and endogenously synthesized lipoic acid in E. coli cells, respectively (Morris et al., 1994(Morris et al., , 1995. LplA protein is involved...

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

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Biosynthesis of Lipoic Acid in Arabidopsis: Cloning and Characterization of the cDNA for Lipoic Acid Synthase

Yasuno

Wada

1998

Plant Physiology

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“…While we cannot entirely exclude the possible presence of a small fraction of HNE-modified peptides in our preparations, limited bias caused by HNE would not weaken but even strengthen our argumentation. H protein of GDC is the dominant lipoylated protein in photosynthesizing plant cells and occurs in large amounts in green leaf mitochondria, representing the major sink for octanoyl chains in these organelles (Wada et al, 1997;Gueguen et al, 2000;Taylor et al, 2004). On the other hand, roots contain only very small amounts of GDC (Douce et al, 2001) and do not require high levels of lipoate biosynthesis.…”

Section: Mtkas Is Important But Not Obligatory For Lipoylation Of Mitmentioning

confidence: 99%

“…Here, we report on the identification of the gld1 locus (now designated mtkas-1) and show that it resides on gene At2g04540 encoding b-ketoacyl-[acyl carrier protein (ACP)] synthase (mtKAS; EC 2.3.1.41), a key enzyme of mitochondrial fatty acid biosynthesis (Wada et al, 1997;Gueguen et al, 2000;Yasuno et al, 2004). One of the major products of mtKAS, octanoyl-ACP, is required for the lipoylation of essential mitochondrial proteins including the H protein of GDC and the dihydrolipoyl acyltransferase (E2) subunits of the pyruvate dehydrogenase (PDH) and a-ketoglutarate dehydrogenase (KGDH) multienzyme complexes.…”

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Mitochondrial Protein Lipoylation Does Not Exclusively Depend on the mtKAS Pathway of de Novo Fatty Acid Synthesis in Arabidopsis

et al. 2007

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The photorespiratory Arabidopsis (Arabidopsis thaliana) mutant gld1 (now designated mtkas-1) is deficient in glycine decarboxylase (GDC) activity, but the exact nature of the genetic defect was not known. We have identified the mtkas-1 locus as gene At2g04540, which encodes b-ketoacyl-[acyl carrier protein (ACP)] synthase (mtKAS), a key enzyme of the mitochondrial fatty acid synthetic system. One of its major products, octanoyl-ACP, is regarded as essential for the intramitochondrial lipoylation of several proteins including the H-protein subunit of GDC and the dihydrolipoamide acyltransferase (E2) subunits of two other essential multienzyme complexes, pyruvate dehydrogenase and a-ketoglutarate dehydrogenase. This view is in conflict with the fact that the mtkas-1 mutant and two allelic T-DNA knockout mutants grow well under nonphotorespiratory conditions. Although on a very low level, the mutants show residual lipoylation of H protein, indicating that the mutation does not lead to a full functional knockout of GDC. Lipoylation of the pyruvate dehydrogenase and a-ketoglutarate dehydrogenase E2 subunits is distinctly less reduced than that of H protein in leaves and remains unaffected from the mtKAS knockout in roots. These data suggest that mitochondrial protein lipoylation does not exclusively depend on the mtKAS pathway of lipoate biosynthesis in leaves and may occur independently of this pathway in roots.

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Lipid Metabolism

Schmid

2004

Handbook of Plant Biotechnology

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Lipids are an immensely diverse group of compounds, technically including all biomolecules that dissolve more readily in non‐polar solvents than in water. This review will emphasisze two prominent groups of lipids: the acyl lipids, whose hydrophobic units are derived from fatty acids, and the isoprenoids, made up of five‐carbon isopentene units. Acyl lipids, in the form of the triacylglycerols stored as energy reserves, underpin the vegetable oil industry. In addition, acyl lipids that dominate the bilayers of plant membranes, are indispensable for the protective layers that prevent plant desiccation and pathogen attack, and include several signalling molecules. Isoprenoids are even more diverse than acyl lipids, with more than 25,000known. Two prominent groups are the sterols, which are important membrane constituents, and the carotenoids, which collect light for photosynthesis, protect plants from excessive light, attract pollinators and fruit dispersal agents, and provide vitamin A precursors for consumers. Biotechnology has provided both a tool for understanding plant lipid metabolism, and a means of altering quality and quantity of these constituents to better serve the needs of industry and human nutrition better.

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Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic acid production

Abstract: The function of acyl carrier protein (ACP) in mitochondria isolated from pea leaves has been investigated.

Cited by 201 publications

References 43 publications

Biosynthesis of Lipoic Acid in Arabidopsis: Cloning and Characterization of the cDNA for Lipoic Acid Synthase

Biosynthesis of Lipoic Acid in Arabidopsis: Cloning and Characterization of the cDNA for Lipoic Acid Synthase

Mitochondrial Protein Lipoylation Does Not Exclusively Depend on the mtKAS Pathway of de Novo Fatty Acid Synthesis in Arabidopsis

Lipid Metabolism

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