Affinage

MRPL45

Large ribosomal subunit protein mL45 · UniProt Q9BRJ2

Length
306 aa
Mass
35.4 kDa
Annotated
2026-06-10
11 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MRPL45 (yeast Mba1/mL45) is a peripheral inner mitochondrial membrane protein that couples mitochondrial translation to cotranslational membrane insertion of respiratory chain subunits (PMID:8690083, PMID:16601683). It is required for respiratory chain biogenesis, and its loss reduces cytochrome b and aa3 levels while producing a partial respiratory growth defect; it associates with the inner membrane through carbonate-extractable, peripheral binding (PMID:8690083). Mechanistically, MRPL45 acts as a ribosome receptor that binds the large subunit of the mitochondrial ribosome and cooperates with the C-terminal ribosome-binding domain of Oxa1 to position the ribosomal exit site at the inner-membrane insertion machinery; loss of both MRPL45 and the Oxa1 C-terminus leaves nascent translation products uninserted and routes them to matrix Hsp70 (PMID:11381092, PMID:16601683). It contacts translation products and conservatively sorted nuclear-encoded proteins during their integration, defining an Oxa1-independent insertion route with overlapping substrate specificity, a role shared with the inner membrane protein Mrx15 (PMID:11381092, PMID:30091672). Beyond insertion, MRPL45 stabilizes a Cox20-ribosome complex in a Cox2-dependent manner and escorts nascent Cox2 toward the Cox18 tail-export machinery without joining the Cox20-Cox18 complex (PMID:27550809). Independent of ribosome membrane tethering, MRPL45 also functions with Mdm38 to regulate translation of selected mitochondrial mRNAs, including Cox1 and cytochrome b (PMID:20427570).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 1996 Medium

    Established that MRPL45/Mba1 is a peripheral inner membrane protein needed for respiratory chain assembly, framing it as a biogenesis factor rather than a structural ribosomal component.

    Evidence Multicopy suppressor screen, gene disruption, c-myc tagging and subcellular fractionation in yeast

    PMID:8690083

    Open questions at the time
    • Did not define molecular partners or the step in biogenesis affected
    • Mode of membrane association characterized only operationally by extraction behavior
  2. 2001 High

    Showed MRPL45 contacts mitochondrial translation products and nuclear-encoded conservatively sorted proteins during membrane integration, placing it in an Oxa1-independent insertion pathway and answering what process it serves.

    Evidence Co-IP/pulldown of translation products, double-mutant genetic analysis, import assays

    PMID:11381092

    Open questions at the time
    • Did not resolve whether interaction with ribosomes is direct or via nascent chains
    • Substrate selectivity versus Oxa1 not fully delineated
  3. 2006 High

    Defined the molecular role as a ribosome receptor binding the mitoribosome large subunit and cooperating with the Oxa1 C-terminus to align the exit tunnel with the insertion machinery.

    Evidence Ribosome-binding Co-IP, double-mutant analysis, Hsp70 substrate trapping in yeast

    PMID:16601683

    Open questions at the time
    • Structural basis of ribosome contact not resolved
    • Functional redundancy with other receptors not yet identified
  4. 2010 High

    Separated MRPL45's ribosome-tethering role from a distinct translation-regulatory function, showing that combined loss with Mdm38 mis-regulates Cox1 and cytochrome b mRNA translation independent of ribosome membrane binding.

    Evidence Double-mutant analysis, ribosome-membrane fractionation, mRNA chimera rescue experiments

    PMID:20427570

    Open questions at the time
    • Molecular basis of mRNA-specific regulation unknown
    • Whether MRPL45 binds the regulatory mRNA regions directly not established
  5. 2016 High

    Connected MRPL45 to a specific maturation pathway by showing it stabilizes a Cox20-ribosome complex and escorts nascent Cox2 toward the Cox18 export machinery without entering the Cox20-Cox18 step.

    Evidence Co-IP, mass spectrometry, Cox18 genetic perturbation, ribosome-nascent chain pulldown

    PMID:27550809

    Open questions at the time
    • Hand-off mechanism between insertion and Cox18 export not structurally defined
    • Whether this role generalizes beyond Cox2 unclear
  6. 2018 High

    Showed MRPL45 acts in parallel with the inner membrane protein Mrx15, both contacting the large ribosomal subunit via soluble C-terminal domains, establishing a redundant network organizing cotranslational membrane protein biogenesis.

    Evidence Systematic MS interaction screen, Co-IP, translation product cross-linking

    PMID:30091672

    Open questions at the time
    • Division of labor between MRPL45 and Mrx15 across substrates not resolved
    • Structural arrangement of the combined ribosome-membrane interface unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MRPL45 mechanistically distinguishes its ribosome-tethering insertion function from its mRNA-selective translation-regulatory function, and the structural basis of its ribosome and membrane contacts, remain open.
  • No structure of MRPL45 on the mitoribosome at the insertion site
  • Direct mRNA or regulatory-factor binding not demonstrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0045182 translation regulator activity 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 1
Partners
COX18COX20MDM38MRX15OXA1
Complex memberships
Cox20-ribosome complexmitochondrial large ribosomal subunit

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Mba1 (MRPL45) is a mitochondrial inner membrane-associated protein required for biogenesis of the respiratory chain; its overexpression suppresses afg3-null and rca1-null mutations, and its disruption leads to reduced cytochrome b and aa3 levels and a partial respiratory growth defect. The protein is extractable by carbonate but not high salt, indicating peripheral membrane association. Genetic epistasis (multicopy suppressor screen), gene disruption, c-myc tagging and subcellular fractionation FEBS letters Medium 8690083
2001 Mba1 (MRPL45) specifically interacts with mitochondrial translation products and with conservatively sorted, nuclear-encoded proteins during their integration into the inner membrane; it functions as part of the mitochondrial protein export machinery in an Oxa1-independent insertion pathway, with overlapping substrate specificity with Oxa1. Co-immunoprecipitation/pulldown of translation products, genetic interaction analysis (double mutants), import assays The Journal of cell biology High 11381092
2006 Mba1 (MRPL45) binds to the large subunit of mitochondrial ribosomes via the inner membrane, functioning as a ribosome receptor that cooperates with the C-terminal ribosome-binding domain of Oxa1 to position the ribosome exit site at the inner membrane insertion machinery. In the absence of both Mba1 and the Oxa1 C-terminus, mitochondrial translation products fail to be properly inserted and become substrates of the matrix chaperone Hsp70. Co-immunoprecipitation (ribosome binding), double mutant analysis, Hsp70 substrate trapping The EMBO journal High 16601683
2010 Simultaneous loss of Mba1 (MRPL45) and Mdm38 causes severe defects in biogenesis of cytochrome reductase and cytochrome oxidase due to mis-regulation of Cox1 and cytochrome b mRNA translation, not due to impaired membrane binding of ribosomes; the Cox1 expression defect is rescued by replacing Cox1-specific mRNA regulatory regions, indicating Mba1 and Mdm38 have overlapping regulatory functions in translation of selected mitochondrial mRNAs. Double mutant analysis, ribosome-membrane fractionation, mRNA chimera rescue experiments Molecular biology of the cell High 20427570
2016 Mba1 (MRPL45) forms a complex with the scaffold protein Cox20 and translating mitochondrial ribosomes in a Cox2-dependent manner; Mba1 stabilizes the Cox20-ribosome complex and supports cotranslational maturation and handover of nascent Cox2 to the Cox18 tail-export machinery. Mba1 is absent from the Cox20-Cox18 complex, indicating it escorts Cox2 from the insertion machinery to maturing assembly intermediates but does not accompany the C-terminal export step. Co-immunoprecipitation, mass spectrometry, genetic interaction (Cox18 loss-of-function), ribosome-nascent chain pull-down Molecular and cellular biology High 27550809
2018 Mba1 (MRPL45) and the newly identified inner membrane protein Mrx15 both interact via soluble C-terminal domains with the large ribosomal subunit and contact mitochondrial translation products during synthesis; they play overlapping roles in cotranslational protein insertion, together organizing membrane protein biogenesis in mitochondria. Systematic mass spectrometry-based interaction screen, co-immunoprecipitation, translation product cross-linking Molecular biology of the cell High 30091672

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Mba1, a membrane-associated ribosome receptor in mitochondria. The EMBO journal 120 16601683
2001 Mba1, a novel component of the mitochondrial protein export machinery of the yeast Saccharomyces cerevisiae. The Journal of cell biology 81 11381092
2010 Ribosome-binding proteins Mdm38 and Mba1 display overlapping functions for regulation of mitochondrial translation. Molecular biology of the cell 53 20427570
2018 The ribosome receptors Mrx15 and Mba1 jointly organize cotranslational insertion and protein biogenesis in mitochondria. Molecular biology of the cell 28 30091672
2006 Tissue inhibitor of matrix metalloproteinase-1 suppresses apoptosis of mouse bone marrow stromal cell line MBA-1. Calcified tissue international 21 16691494
1996 MBA1 encodes a mitochondrial membrane-associated protein required for biogenesis of the respiratory chain. FEBS letters 19 8690083
2023 Mitochondrial Membrane-Associated Protein Mba1 Confers Antifungal Resistance by Affecting the Production of Reactive Oxygen Species in Aspergillus fumigatus. Antimicrobial agents and chemotherapy 18 37428039
2016 Ribosome-Associated Mba1 Escorts Cox2 from Insertion Machinery to Maturing Assembly Intermediates. Molecular and cellular biology 18 27550809
2023 The Mba1 homologue of Trypanosoma brucei is involved in the biogenesis of oxidative phosphorylation complexes. Molecular microbiology 8 36829306
2017 [Genome analysis of Acidiplasma sp. MBA-1, a polyextremophilic archaeon predominant in the microbial community of a bioleaching reactor]. Mikrobiologiia 3 30207146
2006 [Apoptosis of mesenchymal cell line MBA-1 induced by core binding factor alpha 1]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 0 16562667

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