title: AAE13 encodes a dual-localized malonyl-CoA synthetase that is crucial for mitochondrial fatty acid biosynthesis.
abstract: Malonyl-CoA is a key intermediate in a number of metabolic processes associated with its role as a substrate in acylation and condensation reactions. These types of reactions occur in plastids, the cytosol and mitochondria, and although carboxylation of acetyl-CoA is the known mechanism for generating the distinct plastidial and cytosolic pools, the metabolic origin of the mitochondrial malonyl-CoA pool is still unclear. In this study we demonstrate that malonyl-CoA synthetase encoded by the Arabidopsis AAE13 (AT3G16170) gene is localized in both the cytosol and the mitochondria. These isoforms are translated from two types of transcripts, one that contains and one that does not contain a mitochondrial-targeting pre-sequence. Whereas the cytosolic AAE13 protein is not essential, due to the presence of a redundant malonyl-CoA generating system provided by a cytosolic acetyl-CoA carboxylase, the mitochondrial AAE13 protein is essential for plant growth. Phenotypes of the aae13-1 mutant are transgenically reversed only if the mitochondrial pre-sequence is present in the ectopically expressed AAE13 proteins. The aae13-1 mutant exhibits typical metabolic phenotypes associated with a deficiency in the mitochondrial fatty acid synthase system, namely depleted lipoylation of the H subunit of the photorespiratory enzyme glycine decarboxylase, increased accumulation of glycine and glycolate and reduced levels of sucrose. Most of these metabolic alterations, and associated morphological changes, are reversed when the aae13-1 mutant is grown in a non-photorespiratory condition (i.e. a 1% CO2 atmosphere), demonstrating that they are a consequence of the deficiency in photorespiration due to the inability to generate lipoic acid from mitochondrially synthesized fatty acids.
authors.affiliation: Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.|The NSF Engineering Research Center for Biorenewable Chemicals (CBiRC), Iowa State University, Ames, IA, 50011, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA, 50011, USA.|The NSF Engineering Research Center for Biorenewable Chemicals (CBiRC), Iowa State University, Ames, IA, 50011, USA.|Center for Metabolic Biology, Iowa State University, Ames, IA, 50011, USA.
authors.forename: Basil J
authors.initials: BJ
authors.lastname: Nikolau
mesh_terms: D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D005227:Fatty Acids / Q000096:biosynthesis*; D020869:Gene Expression Profiling / Q000379:methods; D018506:Gene Expression Regulation, Plant; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008314:Malonates / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009154:Mutation; D030821:Plants, Genetically Modified; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
chemical_list: D029681:Arabidopsis Proteins; D001426:Bacterial Proteins; D005227:Fatty Acids; D008314:Malonates; D049452:Green Fluorescent Proteins; C030290:malonic acid; D003066:Coenzyme A Ligases; C021533:malonyl-CoA synthetase
keywords: Arabidopsis thaliana; glycine decarboxylase; lipoic acid; malonyl-CoA synthetase; mitochondrial fatty acid synthase; photorespiration