Cytidine diphosphate diacylglycerol synthase is essential for mitochondrial structure and energy production in Arabidopsis thaliana.

SUMMARY: Cytidine diphosphate diacylglycerol (CDP‐DAG), an important intermediate for glycerolipid biosynthesis, is synthesized under the catalytic activity of CDP‐DAG synthase (CDS) to produce anionic phosphoglycerolipids such as phosphatidylglycerol (PG) and cardiolipin (CL). Previous studies showed that Arabidopsis CDSs are encoded by a small gene family, termed CDS1–CDS5, the members of which are integral membrane proteins in endoplasmic reticulum (ER) and in plastids. However, the details on how CDP‐DAG is provided for mitochondrial membrane‐specific phosphoglycerolipids are missing. Here we present the identification of a mitochondrion‐specific CDS, designated CDS6. Enzymatic activity of CDS6 was demonstrated by the complementation of CL synthesis in the yeast CDS‐deficient tam41Δ mutant. The Arabidopsis cds6 mutant lacking CDS6 activity showed decreased mitochondrial PG and CL biosynthesis capacity, a severe growth deficiency finally leading to plant death. These defects were rescued partly by complementation with CDS6 or supplementation with PG and CL. The ultrastructure of mitochondria in cds6 was abnormal, missing the structures of cristae. The degradation of triacylglycerol (TAG) in lipid droplets and starch in chloroplasts in the cds6 mutant was impaired. The expression of most differentially expressed genes involved in the mitochondrial electron transport chain was upregulated, suggesting an energy‐demanding stage in cds6. Furthermore, the contents of polar glycerolipids in cds6 were dramatically altered. In addition, cds6 seedlings lost the capacity for cell proliferation and showed a higher oxidase activity. Thus, CDS6 is indispensable for the biosynthesis of PG and CL in mitochondria, which is critical for establishing mitochondrial structure, TAG degradation, energy production and seedling development. Significance Statement: The Arabidopsis mitochondrial CDP‐DAG synthase, CDS6, differs from the previously identified CDS1–CDS5. CDS6 is indispensable for the biosynthesis of PG and CL in mitochondria, which is critical for establishing the cristae structure of the mitochondrial inner envelope. The Arabidopsis cds6 mutant lacking CDS6 activity showed decreased capacity for TAG degradation and energy production and severe growth deficiency, finally leading to plant death. [ABSTRACT FROM AUTHOR]