[{"date_published":"2020-01-06T00:00:00Z","author":[{"last_name":"Rampelt","first_name":"Heike","full_name":"Rampelt, Heike"},{"first_name":"Iva","full_name":"Sucec, Iva","last_name":"Sucec"},{"last_name":"Bersch","first_name":"Beate","full_name":"Bersch, Beate"},{"full_name":"Horten, Patrick","first_name":"Patrick","last_name":"Horten"},{"first_name":"Inge","full_name":"Perschil, Inge","last_name":"Perschil"},{"first_name":"Jean-Claude","full_name":"Martinou, Jean-Claude","last_name":"Martinou"},{"last_name":"van der Laan","first_name":"Martin","full_name":"van der Laan, Martin"},{"last_name":"Wiedemann","full_name":"Wiedemann, Nils","first_name":"Nils"},{"orcid":"0000-0002-9350-7606","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","last_name":"Schanda","full_name":"Schanda, Paul","first_name":"Paul"},{"full_name":"Pfanner, Nikolaus","first_name":"Nikolaus","last_name":"Pfanner"}],"_id":"8402","oa":1,"type":"journal_article","doi":"10.1186/s12915-019-0733-6","language":[{"iso":"eng"}],"year":"2020","publisher":"Springer Nature","article_type":"original","volume":18,"month":"01","publication_identifier":{"issn":["1741-7007"]},"quality_controlled":"1","extern":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","intvolume":"        18","keyword":["Biotechnology","Plant Science","General Biochemistry","Genetics and Molecular Biology","Developmental Biology","Cell Biology","Physiology","Ecology","Evolution","Behavior and Systematics","Structural Biology","General Agricultural and Biological Sciences"],"article_number":"2","date_created":"2020-09-17T10:26:53Z","pmid":1,"day":"06","publication_status":"published","oa_version":"Published Version","abstract":[{"lang":"eng","text":"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.\r\nResults: 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.\r\nConclusions: 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."}],"status":"public","date_updated":"2021-01-12T08:19:02Z","publication":"BMC Biology","title":"The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments","external_id":{"pmid":["31907035"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1186/s12915-019-0733-6"}],"citation":{"chicago":"Rampelt, Heike, Iva Sucec, Beate Bersch, Patrick Horten, Inge Perschil, Jean-Claude Martinou, Martin van der Laan, Nils Wiedemann, Paul Schanda, and Nikolaus Pfanner. “The Mitochondrial Carrier Pathway Transports Non-Canonical Substrates with an Odd Number of Transmembrane Segments.” <i>BMC Biology</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1186/s12915-019-0733-6\">https://doi.org/10.1186/s12915-019-0733-6</a>.","ieee":"H. Rampelt <i>et al.</i>, “The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments,” <i>BMC Biology</i>, vol. 18. Springer Nature, 2020.","apa":"Rampelt, H., Sucec, I., Bersch, B., Horten, P., Perschil, I., Martinou, J.-C., … Pfanner, N. (2020). The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments. <i>BMC Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s12915-019-0733-6\">https://doi.org/10.1186/s12915-019-0733-6</a>","short":"H. Rampelt, I. Sucec, B. Bersch, P. Horten, I. Perschil, J.-C. Martinou, M. van der Laan, N. Wiedemann, P. Schanda, N. Pfanner, BMC Biology 18 (2020).","mla":"Rampelt, Heike, et al. “The Mitochondrial Carrier Pathway Transports Non-Canonical Substrates with an Odd Number of Transmembrane Segments.” <i>BMC Biology</i>, vol. 18, 2, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1186/s12915-019-0733-6\">10.1186/s12915-019-0733-6</a>.","ista":"Rampelt H, Sucec I, Bersch B, Horten P, Perschil I, Martinou J-C, van der Laan M, Wiedemann N, Schanda P, Pfanner N. 2020. The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments. BMC Biology. 18, 2.","ama":"Rampelt H, Sucec I, Bersch B, et al. The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments. <i>BMC Biology</i>. 2020;18. doi:<a href=\"https://doi.org/10.1186/s12915-019-0733-6\">10.1186/s12915-019-0733-6</a>"}},{"date_updated":"2021-11-26T11:54:29Z","status":"public","oa_version":"Published Version","publication_status":"published","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"22","abstract":[{"text":"Background\r\nESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck. It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Distinct from other cytoskeletal filaments, ESCRT-III filaments do not consume energy themselves, but work in conjunction with another ATP-consuming complex. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling.\r\nResults\r\nHere we present a minimal coarse-grained model that captures all the experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of downward and upward cones and tubules. This model suggests that a change in the geometry of membrane bound ESCRT-III filaments—from a flat spiral to a 3D helix—drives membrane deformation. We then show that such repetitive filament geometry transitions can induce the fission of cargo-containing vesicles.\r\nConclusions\r\nOur model provides a general physical mechanism that explains the full range of ESCRT-III-dependent membrane remodelling and scission events observed in cells. This mechanism for filament force production is distinct from the mechanisms described for other cytoskeletal elements discovered so far. The mechanistic principles revealed here suggest new ways of manipulating ESCRT-III-driven processes in cells and could be used to guide the engineering of synthetic membrane-sculpting systems.","lang":"eng"}],"citation":{"apa":"Harker-Kirschneck, L., Baum, B., &#38; Šarić, A. (2019). Changes in ESCRT-III filament geometry drive membrane remodelling and fission in silico. <i>BMC Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s12915-019-0700-2\">https://doi.org/10.1186/s12915-019-0700-2</a>","ista":"Harker-Kirschneck L, Baum B, Šarić A. 2019. Changes in ESCRT-III filament geometry drive membrane remodelling and fission in silico. BMC Biology. 17(1), 82.","mla":"Harker-Kirschneck, Lena, et al. “Changes in ESCRT-III Filament Geometry Drive Membrane Remodelling and Fission in Silico.” <i>BMC Biology</i>, vol. 17, no. 1, 82, Springer Nature, 2019, doi:<a href=\"https://doi.org/10.1186/s12915-019-0700-2\">10.1186/s12915-019-0700-2</a>.","short":"L. Harker-Kirschneck, B. Baum, A. Šarić, BMC Biology 17 (2019).","ama":"Harker-Kirschneck L, Baum B, Šarić A. Changes in ESCRT-III filament geometry drive membrane remodelling and fission in silico. <i>BMC Biology</i>. 2019;17(1). doi:<a href=\"https://doi.org/10.1186/s12915-019-0700-2\">10.1186/s12915-019-0700-2</a>","chicago":"Harker-Kirschneck, Lena, Buzz Baum, and Anđela Šarić. “Changes in ESCRT-III Filament Geometry Drive Membrane Remodelling and Fission in Silico.” <i>BMC Biology</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1186/s12915-019-0700-2\">https://doi.org/10.1186/s12915-019-0700-2</a>.","ieee":"L. Harker-Kirschneck, B. Baum, and A. Šarić, “Changes in ESCRT-III filament geometry drive membrane remodelling and fission in silico,” <i>BMC Biology</i>, vol. 17, no. 1. Springer Nature, 2019."},"issue":"1","scopus_import":"1","has_accepted_license":"1","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/559898","open_access":"1"}],"publication":"BMC Biology","external_id":{"pmid":["31640700"]},"file":[{"relation":"main_file","content_type":"application/pdf","access_level":"open_access","creator":"cchlebak","date_updated":"2021-11-26T11:37:54Z","success":1,"file_id":"10356","date_created":"2021-11-26T11:37:54Z","checksum":"31d8bae55a376d30925f53f7e1a02396","file_size":1648926,"file_name":"2019_BMCBio_Harker_Kirschneck.pdf"}],"title":"Changes in ESCRT-III filament geometry drive membrane remodelling and fission in silico","language":[{"iso":"eng"}],"doi":"10.1186/s12915-019-0700-2","publisher":"Springer Nature","year":"2019","type":"journal_article","author":[{"full_name":"Harker-Kirschneck, Lena","first_name":"Lena","last_name":"Harker-Kirschneck"},{"full_name":"Baum, Buzz","first_name":"Buzz","last_name":"Baum"},{"last_name":"Šarić","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","orcid":"0000-0002-7854-2139","full_name":"Šarić, Anđela","first_name":"Anđela"}],"oa":1,"_id":"10354","date_published":"2019-10-22T00:00:00Z","date_created":"2021-11-26T11:25:03Z","article_number":"82","pmid":1,"acknowledgement":"We thank Jeremy Carlton, Mike Staddon, Geraint Harker, and the Wellcome Trust Consortium “Archaeal Origins of Eukaryotic Cell Organisation” for fruitful conversations. We thank Peter Wirnsberger and Tine Curk for discussions about the membrane model implementation.","article_processing_charge":"No","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","extern":"1","ddc":["570"],"file_date_updated":"2021-11-26T11:37:54Z","keyword":["cell biology"],"intvolume":"        17","month":"10","quality_controlled":"1","publication_identifier":{"issn":["1741-7007"]},"article_type":"original","volume":17}]