The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments

Abstract: Background
The mitochondrial pyruvate carrier (MPC) plays a central role in energy metabolism by transporting pyruvate across the inner mitochondrial membrane. Its heterodimeric composition and homology to SWEET and semiSWEET transporters set the MPC apart from the canonical mitochondrial carrier family (named MCF or SLC25). The import of the canonical carriers is mediated by the carrier translocase of the inner membrane (TIM22) pathway and is dependent on their structure, which features an even number of transmembrane segments and both termini in the intermembrane space. The import pathway of MPC proteins has not been elucidated. The odd number of transmembrane segments and positioning of the N-terminus in the matrix argues against an import via the TIM22 carrier pathway but favors an import via the flexible presequence pathway.

Results
Here, we systematically analyzed the import pathways of Mpc2 and Mpc3 and report that, contrary to an expected import via the flexible presequence pathway, yeast MPC proteins with an odd number of transmembrane segments and matrix-exposed N-terminus are imported by the carrier pathway, using the receptor Tom70, small TIM chaperones, and the TIM22 complex. The TIM9·10 complex chaperones MPC proteins through the mitochondrial intermembrane space using conserved hydrophobic motifs that are also required for the interaction with canonical carrier proteins.

Conclusions
The carrier pathway can import paired and non-paired transmembrane helices and translocate N-termini to either side of the mitochondrial inner membrane, revealing an unexpected versatility of the mitochondrial import pathway for non-cleavable inner membrane proteins

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
BMC biology. - 18, 1 (2020) , 2, ISSN: 1741-7007

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2020
Creator
Rampelt, Heike
Sucec, Iva
Bersch, Beate
Horten, Patrick
Perschil, Inge
Martinou, Jean-Claude
Laan, Martin van der
Wiedemann, Nils
Schanda, Paul
Pfanner, Nikolaus

DOI
10.1186/s12915-019-0733-6
URN
urn:nbn:de:bsz:25-freidok-1551057
Rights
Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 11:02 AM CEST

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Associated

Time of origin

  • 2020

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