title: Yeast MRX deletions have short chronological life span and more triacylglycerols.
abstract: Saccharomyces cerevisiae is an excellent model organism for lipid research. Here, we have used yeast haploid RAdiation Damage (RAD) deletion strains to study life span and lipid storage patterns. RAD genes are mainly involved in DNA repair mechanism and hence, their deletions have resulted in shorter life span. Viable RAD mutants were screened for non-polar lipid content, and some of the mutants showed significantly high amounts of triacylglycerol (TAG) and steryl ester, besides short chronological life span. Among these, RAD50, MRE11 and XRS2 form a complex, MRX that is involved in homologous recombination that showed an increase in the amount of TAG. Microarray data of single MRX deletions revealed that besides DNA damage signature genes, lipid metabolism genes are also differentially expressed. Lipid biosynthetic genes (LPP1, SLC1) were upregulated and lipid hydrolytic gene (TGL3) was downregulated. We observed that rad50Δ, mre11Δ, xrs2Δ and mrxΔ strains have high number of lipid droplets (LDs) with fragmented mitochondria. These mutants have a short chronological life span compared to wild type. Aged wild-type cells also accumulated TAG with LDs of ∼2.0 μm in diameter. These results suggest that TAG accumulation and big size LDs could be possible markers for premature or normal aging.
authors.affiliation: Lipidomics Center, Central Food Technological Research Institute, Council of Scientific and Industrial Research, Bangalore-560065, India Lipidomics Center, Central Food Technological Research Institute, Council of Scientific and Industrial Research, Mysore-570020, India.
authors.forename: Dhanabalan
authors.initials: D
authors.lastname: Kanagavijayan
authors.affiliation: Lipidomics Center, Central Food Technological Research Institute, Council of Scientific and Industrial Research, Mysore-570020, India.
authors.forename: Ram
authors.initials: R
authors.lastname: Rajasekharan
authors.affiliation: Lipidomics Center, Central Food Technological Research Institute, Council of Scientific and Industrial Research, Bangalore-560065, India The Academy of Scientific and Innovative Research (AcSIR), CSIR-CFTRI, Mysore-570020, India m.srinivasan@cftri.res.in.
authors.forename: Malathi
authors.initials: M
authors.lastname: Srinivasan
mesh_terms: D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D053858:Metabolic Networks and Pathways / Q000235:genetics; D046228:Microarray Analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D014280:Triglycerides; D045643:DNA Repair Enzymes
keywords: RAD deletions; chronological life span; lipid droplet; mitochondrial dysfunction; triacylglycerol