The mitochondrion of Plasmodium falciparum is required for cellular acetyl-CoA metabolism and protein acetylation

Coenzyme A (CoA) biosynthesis is an excellent target for antimalarial intervention. that the mitochondrion is required for cellular acetyl-CoA biosynthesis and identify a synthetic lethal relationship between the two main ketoacid dehydrogenase enzymes. The activity of these enzymes is dependent on the lipoate attachment enzyme LipL2, which is essential for parasite survival solely based on its role in supporting acetyl-CoA metabolism. We also find that acetyl-CoA produced in the mitochondrion is essential for the acetylation of histones and other proteins outside of the mitochondrion. Taken together, our results demonstrate that the mitochondrion is required for cellular acetyl-CoA metabolism and protein acetylation essential for parasite survival.

Automated summary

Coenzyme A (CoA) biosynthesis is a critical target for combating malaria. The study reveals the essential role of the mitochondrion in cellular acetyl-CoA biosynthesis and identifies a synthetic lethal relationship between two key ketoacid dehydrogenase enzymes. The lipoate attachment enzyme LipL2 is found to be crucial for the activity of these enzymes, which is indispensable for parasite survival due to its involvement in acetyl-CoA metabolism. Additionally, the study highlights the importance of mitochondrial-derived acetyl-CoA for protein acetylation outside the mitochondrion. Overall, these findings underscore the significance of the mitochondrion in cellular acetyl-CoA metabolism and protein acetylation crucial for parasite survival.