Mutant/mutation
The mutant lacks expression of PDH E3 (lipoamide dehydrogenase).

Protein (function)
Acetyl-CoA is synthesized from pyruvate by the enzyme complex pyruvate dehydrogenase (PDH). PDH is a member of the α-ketoacid dehydrogenase multienzyme complexes and consists of three subunits: pyruvate dehydrogenase (E1), dihydrolipoyl acetyltransferase (E2) and lipoamide dehydrogenase (dihydrolipoyl dehydrogenase;E3). Acetyl-CoA is an essential precursor of fatty acid synthesis in plastids and fuels the tricarboxylic acid (TCA) cycle in mitochondria, which generates energy in the form of ATP.
In most eukaryotes PDH localizes to the mitochondria where it converts pyruvate into acetyl-CoA and NADH that then enter the TCA cycle for complete oxidization. In plants, a second unique PDH complex is harboured by the plastid and its function is to provide acetyl-CoA for fatty acid synthesis. In Plasmodium there is no evidence for the existence of a mitochondrial PDH complex and the sole Plasmodium PDH complex is targeted to the apicoplast.

In previous studies it has been shown that apicoplast-targeted proteins include enzymes of the FAS II pathway. The presence of this pathway indicates that as well as taking up lipids from its host, Plasmodium also utilizes its own de novo fatty acid synthesis. Transcriptome and proteome analyses of Plasmodium liver stages have demonstrated the expression of apicoplast-targeted enzymes involved in FAS II in liver stages, indicating an important role of de novo FAS II in the developing liver stage. It has been shown that deletion of genes encoding FAS II elongation enzymes (i.e. FabI, FabB/F, FabZ.) caused no defects in parasite blood stage replication and mosquito stage development but livers stage development was severely reduced in the FAS II-deficient parasites.

Phenotype
The phenotype analyses indicate a non-essential role of PDH E3 for blood stages and mosquito stages but an important role during late liver stage development. Analysis of in vitro cultured liver stages showed significant defects in terms of growth and nuclear division. Disruption of  PDH E3 showed a similar phenotype to mutants lacking FAS II elongation enzymes (i.e. FabI, FabB/f; FabZ). This suggests that in Plasmodium the sole function of PDH is to provide the acetyl-CoA necessary for de novo fatty acid synthesis. See also the phenotype of a mutant lacking PDH E1α (pyruvate dehydrogenase E1 alpha subunit; RMgm-376) and an independent mutant lacking expression of PDH E3 (RMgm-379)

Additional information
Mutant parasites develop normal apicoplasts in early liver stages. However, although the apicoplasts were still developing beyond 25 h pi, they developed at a much slower rate when compared with the apicoplast in liver stages of wild type parasites.

Analyses of mutants expressing cmyc-tagged version of PDH E1α (RMgm-371) and PDH E3 (RMgm-372) showed no significant expression in blood stages. PHD E1α-myc and PHD E3-myc expression was observed in mosquito salivary gland sporozoites. The myc-tagged proteins were localized to a small circular structure next to the nucleus. This localization pattern is similar to the localization of epitope-tagged FAS II elongation enzymes that are expressed in the apicoplast . To confirm apicoplast localization of E1α and E3,  an antibody was generated against P. yoelii FabI to be used as an apicoplast marker. IFA analyses demonstated the colocalization of E1α-myc and E3-myc with FabI confirming that PDH, as previously shown for P. falciparum, is exclusively targeted to the apicoplast in P. yoelii. In liver stages E1α-myc staining was observed at 24 hour as tadpole-shaped structures surrounding the dividing nuclei . The complexity of the apicoplast increased after 24 h and exhibited intensive staining at 30 and 43 hi, which coincides with the extensive expansion of the apicoplast during schizogony. At 52 hi, E1α-myc expression appeared as small dots in a similar number and size to the individual nuclei present in the developing merozoites, indicating that each mature merozoite contains an individual apicoplast. IFA analyses of liver stages of parasites expressing  PDH E3-myc showed similar expression patterns. 

Other mutants
RMgm-371: A mutant expressing myc-tagged PDH E1α (pyruvate dehydrogenase E1 alpha subunit)
RMgm-372: A mutant expressing myc-tagged PDH E3
RMgm-376: A mutant lacking expression of PDH E1α (pyruvate dehydrogenase E1 alpha subunit)
RMgm-378: A mutant lacking expression of  PDH E1α and expressing RFP under the constitutive eef1a promoter.
RMgm-379: A mutant lacking expression of  PDH E3 and expressing RFP under the constitutive eef1a promoter.