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In eukaryotes, the biosynthetic pathway for lipoic acid is present in mitochondria. However, it has been hypothesized that, in plants, the biosynthetic pathway is present in plastids in addition to mitochondria. In this study, Arabidopsis thaliana LIP1p cDNA for a plastidial form of lipoic acid synthase has been identified. We show that it encodes a lipoic acid synthase by demonstrating its ability to complement an Escherichia coli mutant lacking lipoic acid synthase activity. We also show that LIP1p is targeted to chloroplasts. These findings suggest that the biosynthetic pathway for lipoic acid is present not only in mitochondria but also in plastids.

Lipoic acid is a coenzyme essential to the activity of enzymes such as pyruvate dehydrogenase, which play important roles in central metabolism. However, neither the enzymes responsible for biosynthesis nor the biosynthetic event of lipoic acid has been reported in mammalian cells. In this study, a mouse mLIP1 cDNA for lipoic acid synthase has been identified. We have shown that the cDNA encodes a lipoic acid synthase by its ability to complement a mutant of Escherichia coli defective in lipoic acid synthase and that mLIP1 is targeted into the mitochondria. These findings suggest that mammalian cells are able to synthesize lipoic acid in mitochondria.

The yeast gene, ACP1, encoding the mitochondrial acyl carrier protein, was deleted by gene replacement. The resulting acp1-deficient mutants had only 5-10% of the wild-type lipoic acid content remaining, and exhibited a respiratory-deficient phenotype. Upon meiosis, the lipoate deficiency co-segregated with the acp1 deletion. The role of ACP1 in long-chain fatty acid synthesis was studied in fast and fas2 null mutants completely lacking cytoplasmic fatty acid synthase. When grown on odd-chain (13:0 and 15:0) fatty acids, these cells showed less than 1% of C-16 and C-18 acids in their total lipids. Mitochondrial ACP is therefore suggested to be involved with the biosynthesis of octanoate, a precursor to lipoic acid.