Dependence of mitochondrial protein translation on anionic phospholipids.
William Dowhan, Xuefeng Su
Biochem. & Mol. Biol., Univ. of Texas Med. Sch., 6431 Fannin St., Houston, TX 77030, USA (william.dowhan@uth.tmc.edu)

In Saccharomyces cerevisiae mutants with a null allele of the PGS1 gene, which results in lack of both phosphatidylglycerol (PG) and cardiolipin (CL) in the mitochondria, the mitochondrial inner membrane proteins encoded by four mitochondrial genes (COX1, COX2, COX3, COB) and one nuclear gene (COX4) are not present. A translation defect rather than a transcription, splicing or import defect appears to account for the lack of these proteins (Ostrander et al. (2001) J. Biol. Chem. 276: 25262-72). To further study the molecular basis of this phenotype, fusions of the 5' UTR's of the COX4 and COX2 genes to reporter genes were constructed. Analysis of deletions of the 120 bp COX4_UTR fused to a GFP or HIS3p reporter expressed in a pgs1 his3 background identified a 50 bp segment responsible for the lack of mRNA translation. Replacement of the mtDNA COX2 gene with a COX2_UTR-ARG8m reporter gene in a pgs1 arg8 mutant resulted in very poor growth in the absence of arginine and very low levels of ARG8p. These results support a requirement for mitochondrial anionic phospholipids for translation of a subset of mitochondrial and nuclear encoded mitochondrial proteins, indicate sensing of mitochondrial functionality by the cytoplasmic translation machinery, and provide a means for identifying complementing genes or suppressors. Funded in part by NIH grant GM56389.

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