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Département Biologie Cellulaire

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  • Vendredi 19 mars 11:00-12:00 - Johannes HERRMANN - Cell Biology, University of Kaiserslautern, Germany

    Mitochondrial protein biogenesis : A huge challenge for eukaryotic cells

    Résumé : Most mitochondrial proteins are synthesized as cytosolic precursor proteins before being imported into mitochondria. The early reactions in the targeting of mitochondrial precursor proteins are largely unclear. We employed a genetic high-throughput screen to identify factors critical for the intracellular sorting of the mitochondrial membrane protein Oxa1. Unexpectedly, we found several components of the ER membrane that are critical for the intracellular transport of Oxa1. By use of a combination of biochemical and genetic approaches, we identified a novel intracellular targeting route for mitochondrial proteins, which directs them to the ER surface where they are maintained in an import-competent conformation. From there, they are handed over to the mitochondrial TOM complex by use of dedicated components, such as the ER-bound J protein Djp1.
    In order to study the response triggered by the cytosolic accumulation of precursor proteins, we employed “clogger” proteins that compete with other precursors. Deep-sequencing of cellular mRNAs upon induction of the “clogger” proteins revealed a global transcriptional program to restore cellular proteostasis. This transcriptional remodeling is a combination of a “wideband” core response that is similar to the general heat shock response and a unique mitoprotein-induced downregulation of the oxidative phosphorylation components. These findings reveal the first comprehensive, time-resolved model of adaptations to mitochondrial import impairment.
    In summary, in my talk I will report about reactions of mitochondrial precursor proteins that occur outside of mitochondria which document novel, so far largely unexplored aspects of cellular biology.

    Contact : Nathalie BONNEFOY (nathalie.bonnefoy

    Lieu : Visio

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