SLS1, A NEW SACCHAROMYCES-CEREVISIAE GENE INVOLVED IN MITOCHONDRIAL METABOLISM, ISOLATED AS A SYNTHETICLETHAL IN ASSOCIATION WITH AN SSM4 DELETION

SSM4 was isolated as a suppressor of rna14-1, a mutant involved in nuc lear mRNA maturation. In order to isolate genes interacting with SSM4, we have searched for mutants that are syntheticlethal in association with an SSM4 deletion. Among the mutants obtained, one, named sls1-1, shows a pet(-) phenotype. We have cloned and sequenced this gene. It e ncodes a protein with a calculated molecular mass of 73 kDa. This prot ein contains a mitochondrial targeting presequence but does not show h omology with other known proteins. Deletion of SLS1 does not affect ce ll viability on glucose but is lethal on a non-fermentable medium. The Sls1p protein does not appear to be involved in mitochondrial DNA rep lication, transcription, or in RNA splicing maturation or stability. W e have also tagged this protein and localized it in mitochondria. Trea tment with alkaline carbonate does not extract this protein from mitoc hondria, suggesting strongly that it is a mitochondrial integral membr ane protein. Thus, the SLS1 gene, encodes a mitochondrial integral mem brane protein and is paradoxically synlethal in association with a del etion of the SSM4 gene, which encodes an integral nuclear membrane pro tein.