PMID:19300474

Citation	Hess, DC, Myers, CL, Huttenhower, C, Hibbs, MA, Hayes, AP, Paw, J, Clore, JJ, Mendoza, RM, Luis, BS, Nislow, C, Giaever, G, Costanzo, M, Troyanskaya, OG and Caudy, AA (2009) Computationally driven, quantitative experiments discover genes required for mitochondrial biogenesis. PLoS Genet. 5:e1000407
Abstract	Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis and inheritance in Saccharomyces cerevisiae. In addition, we used computational predictions to perform targeted double-mutant analysis detecting another nine genes with synthetic defects in mitochondrial biogenesis. This represents an increase of about 25% over previously known participants. Nearly half of these newly characterized proteins are conserved in mammals, including several orthologs known to be involved in human disease. Mutations in many of these genes demonstrate statistically significant mitochondrial transmission phenotypes more subtle than could be detected by traditional genetic screens or high-throughput techniques, and 47 have not been previously localized to mitochondria. We further characterized a subset of these genes using growth profiling and dual immunofluorescence, which identified genes specifically required for aerobic respiration and an uncharacterized cytoplasmic protein required for normal mitochondrial motility. Our results demonstrate that by leveraging computational analysis to direct quantitative experimental assays, we have characterized mutants with subtle mitochondrial defects whose phenotypes were undetected by high-throughput methods.
Links	PubMed PMC2648979 Online version:10.1371/journal.pgen.1000407
Keywords	Cell Respiration/genetics; Cytoplasm/chemistry; Genes, Mitochondrial; Mitochondria/genetics; Mitochondrial Proteins; Mutant Proteins; Mutation; Proteins/genetics; Proteins/physiology; Proteomics; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/growth & development; Saccharomyces cerevisiae/ultrastructure
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:AIM17	involved_in	GO:0007005: mitochondrion organization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
YEAST:AIM21	involved_in	GO:0034642: mitochondrion migration along actin filament	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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