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PMID:19300474

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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

Significance

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


See also

References

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