Project 02:
The role of J-domain proteins in quality control of mitochondrial protein import
Thomas Becker
E-Mail: thbecker@uni-bonn.de
Phone: +49 228-287-2412
Institute of Biochemistry and Molecular Biology
University of Bonn
Janine Kirstein
E-Mail: janine.kirstein@leibniz-fli.de
Phone: +49 3641-656415
Leibniz Institute on Aging
Friedrich-Schiller-University Jena
Abstract
Mitochondria import between 1000 and 1500 proteins that are made as precursors on cytosolic ribosomes. The interplay between mitochondria-bound and cytosolic factors are important to extract non-imported precursor proteins from the mitochondrial protein entry gate, the TOM (translocase of the outer mitochondrial membrane) complex, to deliver them for proteasomal degradation. The cytosolic transport steps are poorly understood. In this project, we will investigate the role of cytosolic J-domain proteins in the quality control of non-imported precursor proteins.
Project-relevant publications
Schulte U, den Brave F, Haupt A, Gupta A, Song J, Müller CS, Engelke J, Mishra S, Mårtensson C, Ellenrieder L, Priesnitz C, Straub SP, Doan KN, Kulawiak B, Bildl W, Rampelt H, Wiedemann N, Pfanner N, Fakler B, Becker T (2023) Mitochondrial complexome reveals quality control pathways of protein import. Nature. 614:153-159.
Song J, Steidle L, Steymans I, Singh J, Sanner A, Böttinger L, Winter D, Becker T (2023) The mitochondrial Hsp70 controls the assembly of the F1FO-ATP synthase. Nat Commun. 14:39.
Ayala Mariscal SM, Pigazzini ML, Richter Y, Özel M, Grothaus IL, Protze J, Ziege K, Kulke M, ElBediwi M, Vermaas JV, Colombi Ciacchi L, Köppen S, Liu F, Kirstein J (2022) Identification of a HTT-specific binding motif in DNAJB1 essential for suppression and disaggregation of HTT. Nat Commun. 13:4692.
Priesnitz C, Böttinger L, Zufall N, Gebert M, Guiard B, van der Laan M, Becker T (2022) Coupling to Pam16 differentially controls the dual role of Pam18 in protein import and respiratory chain formation. Cell Rep. 39:1108619.
Gallrein C, Iburg M, Michelberger T, Koçak A, Puchkov D, Liu F, Ayala Mariscal SM, Nayak T, Kaminski Schierle GS, Kirstein J (2021) Novel amyloid-beta pathology C. elegans model reveals distinct neurons as seeds of pathogenicity. Prog Neurobiol. 198:101907.
Pigazzini ML, Lawrenz M, Margineanu A, Kaminski Schierle GS, Kirstein J (2021) An expanded polyproline domain maintains mutant huntingtin soluble in vivo and during aging. Front Mol Neurosci. 14:721749.
Song J, Herrmann JM, Becker T (2021) Quality control of the mitochondrial proteome. Nat Rev Mol Cell Biol. 22:54-70.
Pigazzini ML, Gallrein C, Iburg M, Kaminski Schierle G, Kirstein J (2020) Characterization of amyloid structures in aging C. elegans using fluorescence lifetime imaging. J Vis Exp. 157:10.3791/61004.
Pigazzini ML, Kirstein J (2020) In vivo quantification of protein turnover in aging C. elegans using photoconvertible dendra2. J Vis Exp. 160:10.3791/61196.
Araiso Y, Tsutsumi A, Qiu J, Imai K, Shiota T, Song J, Lindau C, Wenz LS, Sakaue H, Yunoki K, Kawano S, Suzuki J, Wischnevski M, Schütze C, Ariyama H, Ando T, Becker T, Lithgow T, Wiedemann N, Pfanner N, Kikkawa M, Endo T (2019) Structure of the mitochondrial import gate reveals distinct preprotein paths. Nature. 575:395-401.
Becker T, Song J, Pfanner N (2019) Versatility of preprotein transfer from the cytosol to mitochondria. Trends Cell Biol. 29:534-548.
Mårtensson CU, Priesnitz C, Song J, Ellenrieder L, Doan KN, Boos F, Floerchinger A, Zufall N, Oeljeklaus S, Warscheid B, Becker T (2019) Mitochondrial protein translocation-associated degradation. Nature. 569:679-683.
Opaliński Ł, Song J, Priesnitz C, Wenz LS, Oeljeklaus S, Warscheid B, Pfanner N, Becker T (2018) Recruitment of cytosolic J-proteins by TOM receptors promotes mitochondrial protein biogenesis. Cell Rep. 25:2026-2043.
Kirstein J, Arnsburg K, Scior A, Szlachcic A, Guilbride DL, Morimoto RI, Bukau B, Nillegoda NB (2017) In vivo properties of the disaggregase function of J-proteins and Hsc70 in Caenorhabditis elegans stress and aging. Aging Cell. 16:1414-1424.
Kirstein J, Morito D, Kakihana T, Sugihara M, Minnen A, Hipp MS, Nussbaum-Krammer C, Kasturi P, Hartl FU, Nagata K, Morimoto RI (2015) Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments. EMBO J. 34:2334-2349.
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