Cell and Development Biology

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Nikola Wagener

Mitochondria consist of four subcompartments, the outer membrane, the intermembrane space, the inner membrane and the matrix. They contain their own genome which, in yeast, encodes 8 proteins, most of them are subunits of the respiratory chain complexes. More than 1000 further mitochondrial proteins are encoded in the nuclear genome, synthesized in the cytosol and imported into the different mitochondrial subcompartments. Since proteins of different origin are supposed to assemble later in the same complex with a defined stoichiometry, expression of these proteins has to be tightly regulated in order to avoid cellular stress and energy waste.
We focus on the response to accumulation of unfolded or incorrectly folded proteins within the organelle. Such kind of stress can arise from unbalanced expression of proteins that must assemble into complexes, synthesis and import of altered proteins, damage of mitochondrial DNA, or alterations in transcription/translation. So far, responses to such challenges were observed, but are still understood to a rather limited degree and results obtained from different organisms are often not consistent. In our group yeast is used as a model system due to its excellent accessibility to genetic and biochemical manipulation to investigate the mitochondrial unfolded protein response.