Affinage

MRPL13

Large ribosomal subunit protein uL13m · UniProt Q9BYD1

Length
178 aa
Mass
20.7 kDa
Annotated
2026-06-10
8 papers in source corpus 5 papers cited in narrative 5 extracted findings
Cross-family judge faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MRPL13 is a protein of the mitochondrial ribosomal large subunit that supports oxidative energy metabolism and, beyond its ribosomal role, acts as a regulator of mitochondrial integrity and homeostasis (PMID:7954901, PMID:40841355). It was first defined in yeast, where the gene encodes a large-subunit mitochondrial ribosomal protein imported via an unusually long N-terminal signal peptide, and its disruption impairs growth on non-fermentable carbon sources (PMID:7954901). A non-ribosomal function has since been established: MRPL13 directly binds SLC25A6 (ANT3) and promotes its K48-linked ubiquitin-mediated degradation, thereby restraining mitochondrial permeability transition pore opening, preventing cytochrome c release, and sustaining OXPHOS and ATP output (PMID:40841355). Loss of MRPL13 disrupts mitochondrial homeostasis—causing fragmentation, excessive ROS, and impaired energy metabolism—and triggers compensatory stress responses including mTORC1 activation, the mitochondrial unfolded protein response with depletion of HSP60 and CLPP, and enhanced autophagy (PMID:42062477, PMID:41630109). In cancer contexts MRPL13 promotes proliferation, migration, and survival, acting upstream of PI3K/AKT/mTOR signaling (PMID:33658859).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 1994 Medium

    Established MRPL13 as a bona fide mitochondrial large-subunit ribosomal protein required for respiratory function, answering whether the gene encodes a mitochondrially imported component essential for oxidative metabolism.

    Evidence Gene cloning, N-terminal protein sequencing, and LEU2-insertion disruption with growth phenotyping on non-fermentable carbon sources in yeast

    PMID:7954901

    Open questions at the time
    • Did not address any non-ribosomal or signaling functions
    • Characterized in yeast; human ortholog function not directly tested
    • No structural placement within the ribosomal subunit
  2. 2021 Medium

    Placed MRPL13 upstream of PI3K/AKT/mTOR signaling in cancer, addressing whether the protein influences pro-proliferative signaling beyond a housekeeping ribosomal role.

    Evidence RNAi knockdown in breast cancer cell lines with pAKT/pmTOR Western blots and pharmacological rescue by the PI3K agonist 740Y-P

    PMID:33658859

    Open questions at the time
    • Mechanism linking a ribosomal protein to PI3K activation not defined
    • Single lab, single cancer type
    • No direct molecular partner identified for the signaling effect
  3. 2025 High

    Defined a direct non-ribosomal mechanism whereby MRPL13 protects mitochondrial integrity, answering how MRPL13 loss leads to cell death and metabolic collapse.

    Evidence Co-IP, K48-linkage ubiquitination assays, and knockdown/overexpression in ovarian cancer cells in vitro and in vivo with OXPHOS, ATP, ROS, membrane potential, mPTP, and cytochrome c readouts

    PMID:40841355

    Open questions at the time
    • Identity of the E3 ligase mediating SLC25A6 ubiquitination not defined
    • Relationship between this degradation activity and the ribosomal role unclear
    • Tested in cancer cells; generality to normal tissue not established
  4. 2026 Medium

    Demonstrated in vivo that MRPL13 controls mitochondrial homeostasis upstream of mTORC1 during organ development, linking its loss to a defined developmental phenotype.

    Evidence Zebrafish mrpl13 loss-of-function model with mitochondrial morphology/function assays, mTORC1 activity measurement, and rapamycin rescue of liver developmental defects

    PMID:42062477

    Open questions at the time
    • Molecular step connecting MRPL13 loss to mTORC1 activation unresolved
    • Whether the SLC25A6 axis underlies the developmental phenotype not tested
    • Single model organism
  5. 2026 Medium

    Identified MRPL13 as a regulator of the mitochondrial unfolded protein response, clarifying which stress pathways are engaged when MRPL13 is depleted.

    Evidence siRNA knockdown in HTR8/SVneo and BeWo trophoblast lines with Western blot, immunofluorescence, mitochondrial/migration assays, tunicamycin ER-stress model, and EOPE placenta proteomics

    PMID:41630109

    Open questions at the time
    • Mechanism of UPRmt induction (HSP60/CLPP depletion) not resolved
    • Single lab, trophoblast-specific context
    • Causal link to preeclampsia pathology correlative

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MRPL13's ribosomal role and its non-ribosomal SLC25A6-degradation activity are mechanistically coordinated, and what links its loss to mTORC1 activation, remain unresolved.
  • E3 ligase partner for SLC25A6 ubiquitination unknown
  • Direct molecular trigger of mTORC1 activation undefined
  • No structural model of MRPL13 within the mitoribosome in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005739 mitochondrion 3 GO:0005840 ribosome 1
Pathway
R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-5357801 Programmed Cell Death 1
Partners
SLC25A6
Complex memberships
mitochondrial large ribosomal subunit

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 The yeast nuclear gene MRP-L13 encodes a mitochondrial ribosomal large subunit protein (YmL13) that is imported into mitochondria via an 86-amino-acid N-terminal signal peptide (the longest among known yeast mitochondrial ribosomal proteins). Disruption of MRP-L13 by LEU2 insertion impaired growth on non-fermentable carbon sources, establishing its role in mitochondrial function. Transcription of MRP-L13 is repressed by glucose. Gene cloning, N-terminal protein sequencing, gene disruption (LEU2 insertion), growth phenotype on non-fermentable carbon sources Current genetics Medium 7954901
2021 RNAi-mediated knockdown of MRPL13 in breast cancer cells inhibited proliferation, migration, and EMT-related gene expression, and significantly suppressed phosphorylation of AKT and mTOR; this suppression was partially rescued by the PI3K agonist 740Y-P, placing MRPL13 upstream of PI3K/AKT/mTOR signaling. RNAi knockdown in BC cell lines, Western blot for pAKT/pmTOR, pharmacological rescue with PI3K agonist 740Y-P, proliferation and migration assays Cancer management and research Medium 33658859
2025 MRPL13 specifically interacts with SLC25A6 (ANT3) and promotes its degradation via K48-linked ubiquitination. This interaction inhibits mitochondrial permeability transition pore (mPTP) opening, prevents cytochrome c release into the cytoplasm, and thereby inhibits cell death while enhancing mitochondrial OXPHOS and ATP production in ovarian cancer cells. MRPL13 knockdown caused decreased OXPHOS/ATP, increased ROS, mitochondrial depolarization, aberrant mPTP opening, and mitochondrial structural damage. Co-immunoprecipitation, ubiquitination assay (K48-linkage), MRPL13 knockdown/overexpression in vitro and in vivo, measurement of OXPHOS, ATP, ROS, mitochondrial membrane potential, cytochrome c release, mPTP opening assays Cell death & disease High 40841355
2026 In zebrafish, loss of Mrpl13 disrupts mitochondrial homeostasis (fragmented mitochondria, impaired energy metabolism, excessive ROS, lipid accumulation) and causes liver developmental defects. Loss of Mrpl13 activates mTORC1 signaling, and pharmacological inhibition of mTORC1 with rapamycin significantly rescues the liver developmental defects, placing Mrpl13 upstream of mTORC1 in a regulatory axis controlling mitochondrial homeostasis during liver development. Zebrafish mrpl13 loss-of-function model, mitochondrial morphology and function assays (ROS, energy metabolism, lipid staining), mTORC1 activity measurement, rapamycin rescue experiment, liver developmental phenotype quantification Communications biology Medium 42062477
2026 MRPL13 knockdown in human trophoblast cell lines (HTR8/SVneo and BeWo) triggers the mitochondrial unfolded protein response (UPRmt), depletes HSP60 and CLPP, aggravates mitochondrial dysfunction, inhibits cell migration, and enhances autophagy. Under tunicamycin-induced ER stress, MRPL13 knockdown further depletes HSP60/CLPP and worsens UPRmt, establishing MRPL13 as a regulator of UPRmt in trophoblasts. siRNA knockdown in HTR8/SVneo and BeWo cell lines, Western blotting, immunofluorescence, mitochondrial function assays, migration/proliferation/invasion assays, tunicamycin-induced ER stress model, proteomic sequencing of EOPE placentas Reproduction (Cambridge, England) Medium 41630109

Source papers

Stage 0 corpus · 8 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 MRPL13 Promotes Tumor Cell Proliferation, Migration and EMT Process in Breast Cancer Through the PI3K-AKT-mTOR Pathway. Cancer management and research 36 33658859
2021 MRPL13 Act as a Novel Therapeutic Target and Could Promote Cell Proliferation in Non-Small Cell Lung Cancer. Cancer management and research 20 34285575
1994 The yeast nuclear gene MRP-L13 codes for a protein of the large subunit of the mitochondrial ribosome. Current genetics 15 7954901
2023 Multi-omics analysis of MRPL-13 as a tumor-promoting marker from pan-cancer to lung adenocarcinoma. Aging 13 37827692
2025 MRPL13 enhances mitochondrial function and promotes tumor progression in ovarian cancer by inhibiting mPTP opening via SLC25A6. Cell death & disease 2 40841355
2023 In silico analyses of pan-squamous cell carcinoma unveiled the immunological implications of MRPL13, which had previously been under-recognized. Heliyon 2 38187248
2026 MRPL13 deficiency triggers trophoblast mitochondrial unfolded protein response in early-onset preeclampsia. Reproduction (Cambridge, England) 0 41630109
2026 Mitochondrial protein Mrpl13 regulates zebrafish liver development through the mTORC1-mitochondrial homeostasis pathway. Communications biology 0 42062477

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