Bioinformatický seminár

Tue 6 Dec. 2011, 17:20
I-9

Title: Hess et al. Computationally driven, quantitative experiments discover genes required for mitochondrial biogenesis
Speaker: Martin Bobák, Lukáč Litvaj

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.