Impaired mitochondrial presequence processing causes aggregation of precursor proteins in the matrix Daniel Poveda-Huertes, Stanka Matik, Lisa Myketin, Patrycja Mulica, F.-Nora Vögtle, Chris Meisinger Instituteof Biochemistry and Molecular Biology, Stefan-Meier-Straße 17, D-79104 Freiburg firstname.lastname@example.org
Most mitochondrial proteins are synthesized as precursors in the cytosol and have to be imported into the organelle. 70% of the mitochondrial precursor proteins follow the presequence import pathway using an N-terminal presequence for targeting and translocation into the matrix. Upon entry in the matrix the presequences are cleaved by the Mitochondrial Processing Protease (MPP) leading to mature proteins or processing unstable intermediates that are further cleaved by the proteases Oct1 or Icp55.
In yeast MPP consists of the two subunits Mas1 and Mas2 and both are highly essential for cell life under all conditions. Only little was known so far why presequence cleavage is essential. We therefore systematically analyzed characteristics of immature mitochondrial precursor proteins employing a thermosensitive Mas1 mutant. Inactivation of Mas1 by heat shock in vivo or in organello led to accumulation of non-processed precursor proteins. We find that these precursor proteins are fully imported into Mas1 mutant mitochondria but are largely prone to aggregation when lysed in mild non-ionic detergents. In contrast fully processed precursor proteins are soluble. Aggregation prone precursor proteins accumulating in the mitochondrial matrix are derived from all various functional areas within the organelle including respiration, metabolic enzymes, maintenance and expression of the mtDNA or biosynthesis of iron-sulfur cofactors, a process that makes mitochondria essential in any organism.
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The RTG 2202 “Transport across and into membranes” and the Emmy-Noether program of the DFG fund this study.