title: Retro-translocation of mitochondrial intermembrane space proteins.
abstract: The content of mitochondrial proteome is maintained through two highly dynamic processes, the influx of newly synthesized proteins from the cytosol and the protein degradation. Mitochondrial proteins are targeted to the intermembrane space by the mitochondrial intermembrane space assembly pathway that couples their import and oxidative folding. The folding trap was proposed to be a driving mechanism for the mitochondrial accumulation of these proteins. Whether the reverse movement of unfolded proteins to the cytosol occurs across the intact outer membrane is unknown. We found that reduced, conformationally destabilized proteins are released from mitochondria in a size-limited manner. We identified the general import pore protein Tom40 as an escape gate. We propose that the mitochondrial proteome is not only regulated by the import and degradation of proteins but also by their retro-translocation to the external cytosolic location. Thus, protein release is a mechanism that contributes to the mitochondrial proteome surveillance.
authors.affiliation: Laboratory of Mitochondrial Biogenesis, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland;
authors.forename: Piotr
authors.initials: P
authors.lastname: Bragoszewski
authors.affiliation: Laboratory of Mitochondrial Biogenesis, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland;
authors.forename: Michal
authors.initials: M
authors.lastname: Wasilewski
authors.affiliation: Laboratory of Mitochondrial Biogenesis, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland;
authors.forename: Paulina
authors.initials: P
authors.lastname: Sakowska
authors.affiliation: Laboratory of Mitochondrial Biogenesis, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland;
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gornicka
authors.affiliation: Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung (ZMBZ), Universität Freiburg, 79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany;
authors.forename: Lena
authors.initials: L
authors.lastname: Böttinger
authors.affiliation: Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung (ZMBZ), Universität Freiburg, 79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine, Universität Freiburg, 79104 Freiburg, Germany;
authors.forename: Jian
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung (ZMBZ), Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
authors.affiliation: Laboratory of Mitochondrial Biogenesis, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland; achacinska@iimcb.gov.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
mesh_terms: D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D011487:Protein Conformation; D017510:Protein Folding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: mitochondria; protein biogenesis; protein quality control; protein transport; protein turnover