Callegari 2019 J Mol Biol

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Callegari S, Müller T, Schulz C, Lenz C, Jans DC, Wissel M, Opazo F, Rizzoli SO, Jakobs S, Urlaub H, Rehling P, Deckers M (2019) A MICOS-TIM22 association promotes carrier import into human mitochondria. J Mol Biol 431:2835-51.

» PMID: 31103774 Open Access

Callegari S, Mueller T, Schulz C, Lenz C, Jans DC, Wissel M, Opazo F, Rizzoli SO, Jakobs S, Urlaub H, Rehling P, Deckers M (2019) J Mol Biol

Abstract: 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 towards 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.

Copyright © 2019. Published by Elsevier Ltd.

Keywords: MICOS, Membrane insertion, Mitochondria, Mitochondrial carrier proteins, Mitochondrial import, TIM22, TIM23, Translocase Bioblast editor: Plangger M

Labels: MiParea: Respiration, mt-Membrane, Genetic knockout;overexpression 

Organism: Human  Tissue;cell: HEK  Preparation: Intact cells  Enzyme: Inner mt-membrane transporter 

Coupling state: LEAK, ROUTINE, ET 

HRR: Oxygraph-2k