Motor Recruitment to the TIM23 Channel's Lateral Gate Restricts Polypeptide Release into the Inner Membrane

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Oct 4

PMID 30279421

Citations 15

Authors

Alexander Benjamin Schendzielorz

Piotr Bragoszewski

Nataliia Naumenko

Ridhima Gomkale

Christian Schulz

Bernard Guiard

Agnieszka Chacinska

Peter Rehling

Affiliations

Soon will be listed here.

Abstract

The presequence translocase of the mitochondrial inner membrane (TIM23 complex) facilitates anterograde precursor transport into the matrix and lateral release of precursors with stop-transfer signal into the membrane (sorting). Sorting requires precursor exit from the translocation channel into the lipid phase through the lateral gate of the TIM23 complex. How the two transport modes are regulated and balanced against each other is unknown. Here we show that the import motor J-protein Pam18, which is essential for matrix import, controls lateral protein release into the lipid bilayer. Constitutively translocase-associated Pam18 obstructs lateral precursor transport. Concomitantly, Mgr2, implicated in precursor quality control, is displaced from the translocase. We conclude that during motor-dependent matrix protein transport, the transmembrane segment of Pam18 closes the lateral gate to promote anterograde polypeptide movement. This finding explains why a motor-free form of the translocase facilitates the lateral movement of precursors with a stop-transfer signal.

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References

GLICK B, Brandt A, Cunningham K, Muller S, Hallberg R, Schatz G . Cytochromes c1 and b2 are sorted to the intermembrane space of yeast mitochondria by a stop-transfer mechanism. Cell. 1992; 69(5):809-22. DOI: 10.1016/0092-8674(92)90292-k. View

DSilva P, Schilke B, Walter W, Andrew A, Craig E . J protein cochaperone of the mitochondrial inner membrane required for protein import into the mitochondrial matrix. Proc Natl Acad Sci U S A. 2003; 100(24):13839-44. PMC: 283508. DOI: 10.1073/pnas.1936150100. View

Schleiff E, Becker T . Common ground for protein translocation: access control for mitochondria and chloroplasts. Nat Rev Mol Cell Biol. 2010; 12(1):48-59. DOI: 10.1038/nrm3027. View

Vogtle F, Wortelkamp S, Zahedi R, Becker D, Leidhold C, Gevaert K . Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability. Cell. 2009; 139(2):428-39. DOI: 10.1016/j.cell.2009.07.045. View

Herrmann J, Westermann B, Neupert W . Analysis of protein-protein interactions in mitochondria by coimmunoprecipitation and chemical cross-linking. Methods Cell Biol. 2001; 65:217-30. DOI: 10.1016/s0091-679x(01)65013-1. View

Schendzielorz A, Schulz C, Lytovchenko O, Clancy A, Guiard B, Ieva R . Two distinct membrane potential-dependent steps drive mitochondrial matrix protein translocation. J Cell Biol. 2016; 216(1):83-92. PMC: 5223606. DOI: 10.1083/jcb.201607066. View

Chacinska A, van der Laan M, Mehnert C, Guiard B, Mick D, Hutu D . Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting. Mol Cell Biol. 2009; 30(1):307-18. PMC: 2798301. DOI: 10.1128/MCB.00749-09. View

Ieva R, Schrempp S, Opalinski L, Wollweber F, Hoss P, Heisswolf A . Mgr2 functions as lateral gatekeeper for preprotein sorting in the mitochondrial inner membrane. Mol Cell. 2014; 56(5):641-52. DOI: 10.1016/j.molcel.2014.10.010. View

Ramesh A, Peleh V, Martinez-Caballero S, Wollweber F, Sommer F, van der Laan M . A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import. J Cell Biol. 2016; 214(4):417-31. PMC: 4987294. DOI: 10.1083/jcb.201602074. View

10.

Liu Q, DSilva P, Walter W, Marszalek J, Craig E . Regulated cycling of mitochondrial Hsp70 at the protein import channel. Science. 2003; 300(5616):139-41. DOI: 10.1126/science.1083379. View

11.

Gebert M, Schrempp S, Mehnert C, Heisswolf A, Oeljeklaus S, Ieva R . Mgr2 promotes coupling of the mitochondrial presequence translocase to partner complexes. J Cell Biol. 2012; 197(5):595-604. PMC: 3365495. DOI: 10.1083/jcb.201110047. View

12.

Lytovchenko O, Melin J, Schulz C, Kilisch M, Hutu D, Rehling P . Signal recognition initiates reorganization of the presequence translocase during protein import. EMBO J. 2013; 32(6):886-98. PMC: 3604718. DOI: 10.1038/emboj.2013.23. View

13.

Popov-celeketic D, Waegemann K, Mapa K, Neupert W, Mokranjac D . Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex. EMBO Rep. 2011; 12(6):542-8. PMC: 3128279. DOI: 10.1038/embor.2011.72. View

14.

Truscott K, Voos W, Frazier A, Lind M, Li Y, Geissler A . A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria. J Cell Biol. 2003; 163(4):707-13. PMC: 2173675. DOI: 10.1083/jcb.200308004. View

15.

Oreb M, Tews I, Schleiff E . Policing Tic 'n' Toc, the doorway to chloroplasts. Trends Cell Biol. 2007; 18(1):19-27. DOI: 10.1016/j.tcb.2007.10.002. View

16.

Schulz C, Schendzielorz A, Rehling P . Unlocking the presequence import pathway. Trends Cell Biol. 2014; 25(5):265-75. DOI: 10.1016/j.tcb.2014.12.001. View

17.

Marom M, Safonov R, Amram S, Avneon Y, Nachliel E, Gutman M . Interaction of the Tim44 C-terminal domain with negatively charged phospholipids. Biochemistry. 2009; 48(47):11185-95. DOI: 10.1021/bi900998v. View

18.

Frey S, Gorlich D . The Xenopus laevis Atg4B Protease: Insights into Substrate Recognition and Application for Tag Removal from Proteins Expressed in Pro- and Eukaryotic Hosts. PLoS One. 2015; 10(4):e0125099. PMC: 4414272. DOI: 10.1371/journal.pone.0125099. View

19.

Mokranjac D, Sichting M, Neupert W, Hell K . Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria. EMBO J. 2003; 22(19):4945-56. PMC: 204468. DOI: 10.1093/emboj/cdg485. View

20.

Chacinska A, Lind M, Frazier A, Dudek J, Meisinger C, Geissler A . Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell. 2005; 120(6):817-29. DOI: 10.1016/j.cell.2005.01.011. View