ArticleBMC biology2020
The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments.
Article in BMC biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Evolution and Adaptation of the Mitochondrial Protein Import Machinery in Parasitic Protists: Beyond the Canonical TOM Complex.International journal of molecular sciences · 2026Review
- Mitochondrial and plasma‑membrane transport‑based engineering enables industrial‑level isocitric acid production in Yarrowia lipolytica.Microbial cell factories · 2026Article
- From the cytosol to the inner membrane: biogenesis of the mitochondrial carrier family.Protein science : a publication of the Protein Society · 2026Review
- Biogenesis and function of the mitochondrial solute carrier (SLC25) family in yeast.Biological chemistry · 2025Review
- Molecular machineries and pathways of mitochondrial protein transport.Nature reviews. Molecular cell biology · 2025Review
- Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier.Science advances · 2025Article
- Protein insertion into the inner membrane of mitochondria: routes and mechanisms.FEBS open bio · 2024Review
- TIMM9 as a prognostic biomarker in multiple cancers and its associated biological processes.Scientific reports · 2024Article
- Article
- Mechanisms of mitochondrial respiratory adaptation.Nature reviews. Molecular cell biology · 2022Review
- The mitochondrial protein Sideroflexin 3 (SFXN3) influences neurodegeneration pathways in vivo.The FEBS journal · 2022Article
- Ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) is a novel complex III-specific assembly factor in mitochondria.Molecular biology of the cell · 2022Article
- Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.Cell metabolism · 2021Article
- Structural Insights into the Human Mitochondrial Pyruvate Carrier Complexes.Journal of chemical information and modeling · 2021Article
- Mitochondrial Targeting of the Ammonia-Sensitive Uncoupler SLC4A11 by the Chaperone-Mediated Carrier Pathway in Corneal Endothelium.Investigative ophthalmology & visual science · 2021Article
- Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding Sites in TOM70 and Recruitment of Hsp90.International journal of molecular sciences · 2021Article
- Review
- Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration.Life (Basel, Switzerland) · 2021Review
- The Importance of Mitochondrial Pyruvate Carrier in Cancer Cell Metabolism and Tumorigenesis.Cancers · 2021Review
- The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism.Molecular biology of the cell · 2021Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
resultsHere, 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.
conclusionsThe 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.
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