Presenter: Nitya Subrahmanian, Graduate Student of Molecular Genetics, Hamel Lab
Title: Investigation of the effect of human nuclear mutations on complex I deficiency using Chlamydomonas reinhardtii as a model system
Abstract: Mitochondrial complex I (CI), consisting of more than 40 subunits of dual genetic origin, is the first enzyme required for oxidative phosphorylation. Mutations in genes encoding for CI subunits are the cause of severe metabolic disorders in humans. However, the contribution of many mutations to CI deficiency is not clearly understood. The unicellular alga Chlamydomonas reinhardtii is as an ideal model organism for studying Complex I as complete loss is viable, unlike in mammals, due to alternative enzymes that can bypass Complex I. We delineate the effect of human mutations observed in two subunits, NDUFV2 and NDUFB10, by reconstructing the mutations in Chlamydomonas. In particular, we used the ndufv2- and ndufb10- null mutants, isolated from our forward genetic screen for CI mutants, as a tool for this study by transforming them with the mutant variants of interest and analyzing the resultant CI activity and assembly. Using Chlamydomonas as a model system is advantageous because CI subunits are highly conserved and the complexities of tissue-specific phenotypes, observed in patients, is negated in a unicellular organism.
