A MICOS-TIM22 Association Promotes Carrier Import into Human Mitochondria

2019-07-12 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​A MICOS-TIM22 Association Promotes Carrier Import into Human Mitochondria​
Callegari, S.; Müller, T.; Schulz, C.; Lenz, C.; Jans, D. C; Wissel, M. & Opazo, F. et al.​ (2019) 
Journal of Molecular Biology431(15) pp. 2835​-2851​.​ DOI: https://doi.org/10.1016/j.jmb.2019.05.015 

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Callegari, Sylvie; Müller, Tobias; Schulz, Christian; Lenz, Christof; Jans, Daniel C; Wissel, Mirjam; Opazo, Felipe; Rizzoli, Silvio O. ; Jakobs, Stefan ; Urlaub, Henning; Rehling, Peter ; Deckers, Markus
Mitochondrial membrane proteins with internal targeting signals are inserted into the inner membrane by the carrier translocase (TIM22 complex). For this, precursors have to be initially directed from the TOM complex in the outer mitochondrial membrane across the intermembrane space toward the TIM22 complex. How these two translocation processes are topologically coordinated is still unresolved. Using proteomic approaches, we find that the human TIM22 complex associates with the mitochondrial contact site and cristae organizing system (MICOS) complex. This association does not appear to be conserved in yeast, whereby the yeast MICOS complex instead interacts with the presequence translocase. Using a yeast mic10Δ strain and a HEK293T MIC10 knockout cell line, we characterize the role of MICOS for protein import into the mitochondrial inner membrane and matrix. We find that a physiological cristae organization promotes efficient import via the presequence pathway in yeast, while in human mitochondria, the MICOS complex is dispensable for protein import along the presequence pathway. However, in human mitochondria, the MICOS complex is required for the efficient import of carrier proteins into the mitochondrial inner membrane. Our analyses suggest that in human mitochondria, positioning of the carrier translocase at the crista junction, and potentially in vicinity to the TOM complex, is required for efficient transport into the inner membrane.
Issue Date
Journal of Molecular Biology 
SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente 
SFB 1190 | P01: Untersuchung der Unterschiede in der Zusammensetzung, Funktion und Position von individuellen MICOS Komplexen in einzelnen Säugerzellen 
SFB 1190 | P09: Proteinsortierung in der Synapse: Prinzipien und molekulare Organisation 
SFB 1190 | P13: Protein Transport über den mitochondrialen Carrier Transportweg 
SFB 1190 | Z02: Massenspektrometrie-basierte Proteomanalyse 
Working Group
RG Jakobs (Structure and Dynamics of Mitochondria) 
RG Rehling (Mitochondrial Protein Biogenesis) 
RG Rizzoli (Quantitative Synaptology in Space and Time) 
RG Urlaub (Bioanalytische Massenspektrometrie) 
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