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 c...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-01-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-019-0733-6 |
| _version_ | 1818429481524658176 |
|---|---|
| author | Heike Rampelt Iva Sucec Beate Bersch Patrick Horten Inge Perschil Jean-Claude Martinou Martin van der Laan Nils Wiedemann Paul Schanda Nikolaus Pfanner |
| author_facet | Heike Rampelt Iva Sucec Beate Bersch Patrick Horten Inge Perschil Jean-Claude Martinou Martin van der Laan Nils Wiedemann Paul Schanda Nikolaus Pfanner |
| author_sort | Heike Rampelt |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T15:18:12Z |
| format | Article |
| id | doaj.art-b7ca500a447d438abd73801cf1639dc7 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-14T15:18:12Z |
| publishDate | 2020-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-b7ca500a447d438abd73801cf1639dc72022-12-21T22:56:15ZengBMCBMC Biology1741-70072020-01-0118111410.1186/s12915-019-0733-6The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segmentsHeike Rampelt0Iva Sucec1Beate Bersch2Patrick Horten3Inge Perschil4Jean-Claude Martinou5Martin van der Laan6Nils Wiedemann7Paul Schanda8Nikolaus Pfanner9Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of FreiburgInstitut de Biologie Structurale (IBS), Univ. Grenoble Alpes, CEA, CNRSInstitut de Biologie Structurale (IBS), Univ. Grenoble Alpes, CEA, CNRSInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of FreiburgInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of FreiburgDepartment of Cell Biology, University of GenevaMedical Biochemistry and Molecular Biology, Center for Molecular Signaling, PZMS, Saarland UniversityInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of FreiburgInstitut de Biologie Structurale (IBS), Univ. Grenoble Alpes, CEA, CNRSInstitute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of FreiburgAbstract 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.https://doi.org/10.1186/s12915-019-0733-6Mitochondrial pyruvate carrierMPCMitochondrial protein biogenesisProtein importTIM22 complexTim9 |
| spellingShingle | Heike Rampelt Iva Sucec Beate Bersch Patrick Horten Inge Perschil Jean-Claude Martinou Martin van der Laan Nils Wiedemann Paul Schanda Nikolaus Pfanner The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments BMC Biology Mitochondrial pyruvate carrier MPC Mitochondrial protein biogenesis Protein import TIM22 complex Tim9 |
| title | The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments |
| title_full | The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments |
| title_fullStr | The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments |
| title_full_unstemmed | The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments |
| title_short | The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments |
| title_sort | mitochondrial carrier pathway transports non canonical substrates with an odd number of transmembrane segments |
| topic | Mitochondrial pyruvate carrier MPC Mitochondrial protein biogenesis Protein import TIM22 complex Tim9 |
| url | https://doi.org/10.1186/s12915-019-0733-6 |
| work_keys_str_mv | AT heikerampelt themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT ivasucec themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT beatebersch themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT patrickhorten themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT ingeperschil themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT jeanclaudemartinou themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT martinvanderlaan themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT nilswiedemann themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT paulschanda themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT nikolauspfanner themitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT heikerampelt mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT ivasucec mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT beatebersch mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT patrickhorten mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT ingeperschil mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT jeanclaudemartinou mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT martinvanderlaan mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT nilswiedemann mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT paulschanda mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments AT nikolauspfanner mitochondrialcarrierpathwaytransportsnoncanonicalsubstrateswithanoddnumberoftransmembranesegments |