Affinage

LRPPRC

Leucine-rich PPR motif-containing protein, mitochondrial · UniProt P42704

Length
1394 aa
Mass
157.9 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRPPRC (LRP130) is a metazoan-conserved, mitochondrial matrix PPR-family RNA-binding protein that governs the post-transcriptional fate of the mitochondrial transcriptome (PMID:12832482, PMID:20633537). Acting as a stable heterodimer with SLIRP—formed through interaction between SLIRP's RRM domain and three PPR motifs in LRPPRC, with SLIRP reciprocally protecting LRPPRC from degradation (PMID:27353330, PMID:26247782)—the complex functions as a global RNA chaperone that binds mitochondrial mRNA coding sequences and remodels their secondary structure to expose sites for stabilization, polyadenylation, and translation (PMID:29146908, PMID:22661577). Mechanistically, LRPPRC-SLIRP suppresses PNPase/SUV3-mediated 3' exonucleolytic decay and promotes MTPAP-dependent polyadenylation (PMID:22661577), and the cryo-EM structure shows LRPPRC docking onto mitoribosomal proteins mS39 and mS31 to form a corridor that hands mRNA off to the ribosome, with COX1 and COX2 translation most dependent on this activity (PMID:39134711, PMID:21880015). LRPPRC does not activate mitochondrial transcription (PMID:23599432). Loss of LRPPRC destabilizes most mtDNA-encoded mRNAs, abolishes polyadenylation, and dyscoordinates OXPHOS subunit translation, producing complex IV and ATP synthase deficiency, mitochondrial hyperpolarization and ROS, and an evolutionarily conserved compensatory program of mitochondrial hyperfusion and the mitochondrial unfolded protein response (PMID:22045337, PMID:24399447, PMID:23878239, PMID:26412102). The A354V hypomorphic mutation underlies Leigh syndrome French-Canadian type (LSFC), reducing LRPPRC levels and selectively impairing COX I mRNA stability and translation (PMID:15139850). Outside the matrix, LRPPRC associates with PGC-1α as a transcriptional coactivator required for gluconeogenic and brown-fat thermogenic gene programs (PMID:17050673, PMID:18728005), and acts as a cytoplasmic m6A reader and mRNA-stabilizing factor whose targets include MDR1, CDK6, PD-L1, and LDHA, linking it to chemoresistance, cell-cycle progression, immune evasion, and glycolytic metabolism in cancer (PMID:35484333, PMID:37452037, PMID:37063837, PMID:38372449).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2003 High

    Established that LRPPRC is a bona fide RNA-binding protein localized predominantly to mitochondria, binding mitochondrial polyadenylated RNAs through a non-canonical PPR-containing domain, redirecting attention from a presumed nuclear role to mitochondrial RNA metabolism.

    Evidence In vivo RNA crosslinking/IP, in vitro RNA-binding assays, subcellular fractionation, and domain mapping

    PMID:12832482

    Open questions at the time
    • Did not define which mitochondrial transcripts are functionally regulated
    • RNA-binding domain mapping did not resolve the full PPR architecture's contribution
  2. 2004 Medium

    Linked LRPPRC to human disease by showing the LSFC A354V mutation reduces LRPPRC levels and selectively impairs COX I mRNA stability and translation, establishing a causal mechanism for the cytochrome c oxidase deficiency.

    Evidence Northern blot, [35S]methionine mitochondrial translation labeling, and import assays in LSFC patient cells

    PMID:15139850

    Open questions at the time
    • Did not explain transcript selectivity for COX I
    • Mechanism connecting reduced protein to translation defect unresolved
  3. 2004 Medium

    Identified a nuclear, sequence-specific transcriptional activity of LRP130 on the MDR1 and MVP promoters, the first evidence of an extramitochondrial gene-regulatory role.

    Evidence EMSA, ChIP, luciferase reporters, and siRNA/transcriptional decoys in cell lines

    PMID:15272088

    Open questions at the time
    • Did not reconcile nuclear function with predominantly mitochondrial localization
    • Direct DNA-binding versus cofactor recruitment not distinguished
  4. 2006 High

    Placed LRP130 within the PGC-1α coactivator complex and showed it is required for gluconeogenic gene induction and hepatic glucose output, defining a role in metabolic transcriptional programs.

    Evidence Co-purification/MS of the PGC-1α complex and adenoviral RNAi in fasted mice

    PMID:17050673

    Open questions at the time
    • Did not clarify whether this is a direct DNA-associated function or indirect
    • Relationship to the mitochondrial RNA function unaddressed
  5. 2008 Medium

    Extended the PGC-1α partnership to brown adipose tissue, showing LRP130 is required for UCP1 expression and thermogenic proton leak.

    Evidence Co-IP, knockdown in brown adipocytes, and oxygen consumption assays

    PMID:18728005

    Open questions at the time
    • Direct versus indirect transcriptional contribution not resolved
    • Tissue specificity mechanism unknown
  6. 2010 Medium

    Settled the localization debate by demonstrating LRPPRC is exclusively a mitochondrial matrix protein with a cleaved targeting sequence, constraining models of its nuclear/cytoplasmic functions.

    Evidence Subcellular fractionation and targeting-sequence bioinformatics in mammalian cells

    PMID:20633537

    Open questions at the time
    • Apparent conflict with reported nuclear roles not reconciled
    • Single-isoform claim limits explanation of dual localization
  7. 2011 High

    Defined the core mitochondrial phenotype in vivo: LRPPRC loss collapses steady-state mRNA levels, abolishes polyadenylation, and dyscoordinates translation, establishing it as a master post-transcriptional regulator maintaining a non-translated mRNA pool.

    Evidence Conditional Lrpprc knockout mouse heart with Northern blot, translation assays, and complex analysis

    PMID:22045337

    Open questions at the time
    • Did not resolve molecular activities (chaperone vs. polyadenylation vs. ribosome delivery)
    • Did not identify the partner stabilizing the complex
  8. 2011 Low

    Proposed that LRPPRC complexes with POLRMT to activate mitochondrial transcription, an interpretation later contradicted by more rigorous reconstitution.

    Evidence Single Co-IP, overexpression, and OXPHOS/fatty-acid oxidation assays

    PMID:21971050

    Open questions at the time
    • POLRMT interaction not confirmed and directly contradicted by PMID 23599432
    • No in vitro reconstitution of transcriptional activation
  9. 2012 High

    Mapped two mechanistic activities of the LRPPRC/SLIRP complex—suppression of PNPase/SUV3 degradation and promotion of MTPAP polyadenylation—explaining how it stabilizes mitochondrial mRNAs; a parallel study mapped COX I mRNA binding to the first 19 PPR motifs.

    Evidence In vitro polyadenylation and degradation assays, RIP, and PPR-truncation RNA-binding assays with a gene-trap mouse

    PMID:21880015 PMID:22661577

    Open questions at the time
    • Did not show how the same complex coordinates degradation suppression with translation
    • Structural basis of mRNA handoff to the ribosome not resolved
  10. 2013 High

    Rigorously excluded a transcriptional-activation role inside mitochondria, showing no POLRMT interaction and no activation of in vitro transcription, refocusing the field on post-transcriptional function.

    Evidence Size-exclusion chromatography, multiple Co-IPs, in vitro transcription reconstitution, and transgenic/heterozygous KO mice

    PMID:23599432

    Open questions at the time
    • Effect on precursor transcripts not mechanistically explained
    • Did not address the separate nuclear PGC-1α transcriptional role
  11. 2013 High

    Revealed conserved organellar consequences of LRPPRC loss—mitochondrial hyperfusion as a protective response to low complex IV activity—linking the molecular defect to mitochondrial dynamics.

    Evidence C. elegans mma-1 mutants and mammalian knockdown with live imaging, epistasis, and ATP measurement

    PMID:23878239

    Open questions at the time
    • Signaling pathway connecting OXPHOS deficiency to fusion machinery not defined
    • Whether hyperfusion is adaptive in mammals long-term unclear
  12. 2013 Medium

    Reported extramitochondrial roles in autophagy control via a LRPPRC-Beclin1-Bcl-2 ternary complex, suggesting LRPPRC restrains basal autophagy.

    Evidence Reciprocal Co-IP, GFP-LC3 puncta, LC3-II/p62 westerns, and siRNA in multiple lines

    PMID:23822101

    Open questions at the time
    • How a matrix protein engages cytosolic Beclin1/Bcl-2 unresolved
    • Direct versus membrane-potential-dependent effect not separated
  13. 2014 High

    Broadened the OXPHOS phenotype beyond COX to ATP synthase deficiency with subassembled complexes, hyperpolarization, and ROS, refining the bioenergetic pathology of LRPPRC loss.

    Evidence Conditional Lrpprc KO mouse heart with OXPHOS activity, membrane potential, and ROS measurements

    PMID:24399447

    Open questions at the time
    • Mechanism linking mRNA defects to ATP synthase subassembly not detailed
    • Tissue-specific severity not explained
  14. 2014 Low

    Connected LRPPRC to Parkin-mediated mitophagy under stress, positioning it on the outer membrane interface during mitochondrial turnover.

    Evidence Co-IP, fractionation, and CCCP-induced mitophagy with Parkin/Bcl-2/LC3 westerns

    PMID:24722279

    Open questions at the time
    • Single Co-IP/pulldown without reciprocal structural validation
    • How a matrix protein becomes exposed on the OMM unexplained
  15. 2015 High

    Defined the SLIRP partnership: SLIRP stabilizes LRPPRC and is required for ribosome association and efficient translation but dispensable for polyadenylation, separating the complex's activities.

    Evidence Slirp knockout mice with ribosome-fraction RNA-seq and protein-stability and polyadenylation analyses

    PMID:26247782

    Open questions at the time
    • Structural basis of the heterodimer not yet resolved at this stage
    • Why Slirp KO mice remain healthy despite mRNA loss unexplained
  16. 2016 High

    Provided the biochemical/structural basis of LRPPRC-SLIRP heterodimerization, showing SLIRP RRM RNP1 residues are repurposed for protein-protein contact while LRPPRC carries the broad RNA-binding capacity.

    Evidence In vitro RNA-binding assays, interface mutagenesis, and biochemical complex characterization

    PMID:27353330

    Open questions at the time
    • Did not visualize the complex on RNA or the ribosome
    • Functional consequence of specific interface residues in vivo untested
  17. 2017 High

    Generalized LRPPRC-SLIRP function to a transcriptome-wide RNA chaperone that remodels mitochondrial mRNA secondary structure to expose functional sites, unifying its stabilization, polyadenylation, and translation roles.

    Evidence RNase footprinting combined with PAR-CLIP across the mitochondrial transcriptome

    PMID:29146908

    Open questions at the time
    • Did not provide an atomic model of mRNA handoff
    • Transcript-specific translation effects not yet structurally explained
  18. 2024 High

    Delivered the structural endpoint: cryo-EM of LRPPRC-SLIRP on mRNA and the mitoribosome showing LRPPRC contacts mS39/mS31 to form an mRNA-handoff corridor, with COX1/COX2 most translation-dependent, and an in vivo study showed the complex is required for complex I maintenance with tissue-specific coordination.

    Evidence Cryo-EM with RNA-seq, metabolic labeling, ribosome profiling; plus knock-in/Slirp-KO mice and mtDNA double-mutant epistasis

    PMID:39087558 PMID:39134711

    Open questions at the time
    • Dynamics of repeated mRNA loading/release not captured
    • Tissue specificity of coordination not mechanistically explained
  19. 2024 Medium

    Established a regulated turnover network for LRPPRC, with K453 K48-ubiquitination by STUB1 (controlled upstream by USP44) and stabilization by PSMD14, coupling LRPPRC levels to ROS, apoptosis, and chemosensitivity; SIRT3 deacetylation further tunes its activity.

    Evidence Co-IP, ubiquitination site mapping, deubiquitinase/deacetylase manipulation, and in vivo tumor models

    PMID:36328147 PMID:39215663 PMID:39557134

    Open questions at the time
    • PSMD14 and SIRT3 studies lack mapped sites or are single-Co-IP
    • How matrix-localized LRPPRC accesses cytosolic ubiquitin machinery unresolved
  20. 2024 Medium

    Defined a cytoplasmic m6A-reader function for LRPPRC stabilizing oncogenic mRNAs—PD-L1, LDHA, CDK6, and MDR1—linking it to immune evasion, glycolysis, cell-cycle progression, and chemoresistance.

    Evidence MeRIP-seq/qPCR, RIP, RNA pull-down, mRNA stability and metabolic assays, with xenografts/organoids

    PMID:35484333 PMID:37063837 PMID:37452037 PMID:38372449

    Open questions at the time
    • m6A-site mutagenesis to rigorously confirm reader function not done in several studies
    • How an annotated matrix protein achieves cytoplasmic mRNA binding not reconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LRPPRC partitions between its established mitochondrial matrix RNA-chaperone role and its reported nuclear/cytoplasmic transcriptional and m6A-reader functions remains the central unresolved question.
  • No mechanism for dual subcellular targeting
  • Whether extramitochondrial roles reflect a minor pool or distinct isoform unknown
  • Stoichiometry between PGC-1α coactivation and m6A reading undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 11 GO:0140110 transcription regulator activity 4 GO:0045182 translation regulator activity 3 GO:0044183 protein folding chaperone 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 2
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 2 R-HSA-1643685 Disease 1
Partners
BCL-2BECLIN 1MAVSMTPAPPGC-1ΑPSMD14SLIRPSTUB1
Complex memberships
LRPPRC-SLIRP complexPGC-1α coactivator complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 Cryo-EM structure of LRPPRC-SLIRP complex bound to mRNA and the mitoribosome shows that LRPPRC associates with mitoribosomal proteins mS39 and the N-terminus of mS31 through its helical (PPR) repeats, forming a corridor for mRNA handoff to the ribosome; SLIRP directly binds the mRNA and stabilizes LRPPRC within the complex. RNA sequencing, metabolic labeling, and ribosome profiling show transcript-specific effects on translation efficiency, with COX1 and COX2 translation most affected. Cryo-electron microscopy structure determination, RNA sequencing, metabolic labeling, mitoribosome profiling Nature structural & molecular biology High 39134711
2017 LRPPRC in complex with SLIRP acts as a global RNA chaperone throughout the mitochondrial transcriptome, stabilizing RNA secondary structures to expose sites required for translation, stabilization, and polyadenylation. RNase footprinting combined with PAR-CLIP showed LRPPRC-SLIRP binds preferentially to mRNAs, and its loss alters the entire secondary structure and stability of the mitochondrial transcriptome. RNase footprinting, PAR-CLIP (photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation) Nature communications High 29146908
2016 LRPPRC-SLIRP form a heterodimer via interactions between polar amino acids in the single RRM domain of SLIRP and three neighboring PPR motifs in the second quarter of LRPPRC. Specific residues at this interface, predicted to bind RNA in LRPPRC and located in the RNP1 motif of SLIRP's RRM, are instead used for protein-protein interaction, enabling stable complex formation. In vitro binding assays showed LRPPRC has broad RNA-binding capacity while SLIRP associates only weakly with RNA. In vitro RNA-binding assays, mutagenesis of interaction interface, biochemical characterization of LRPPRC-SLIRP complex Nucleic acids research High 27353330
2011 Tissue-specific knockout of Lrpprc in mouse heart causes drastic reduction in steady-state levels of most mitochondrial mRNAs, loss of mRNA polyadenylation, and aberrant mitochondrial translation with excessive translation of some transcripts and absent translation of others. LRPPRC forms an RNA-dependent protein complex necessary for maintaining a pool of non-translated mRNAs. Conditional knockout mouse model, Northern blot, mitochondrial translation assay, protein complex analysis The EMBO journal High 22045337
2012 The LRPPRC/SLIRP complex suppresses 3' exonucleolytic mRNA degradation mediated by PNPase and SUV3 and cotranscriptionally binds coding sequences of mitochondrial mRNAs. In vitro, LRPPRC promoted polyadenylation of mRNAs mediated by mitochondrial poly(A) polymerase (MTPAP). In vitro polyadenylation assay with MTPAP, RNA degradation assay with PNPase/SUV3, RNA immunoprecipitation, absolute quantification of mitochondrial mRNAs Nucleic acids research High 22661577
2015 SLIRP stabilizes LRPPRC by protecting it from degradation; LRPPRC is partially degraded when the LRPPRC-SLIRP complex is disrupted. SLIRP is required for proper association of mRNAs with the mitochondrial ribosome and efficient translation, but is dispensable for mRNA polyadenylation. Slirp knockout mice show 50–70% reduction in mtDNA-encoded mRNAs despite being apparently healthy. Slirp knockout mice, deep RNA sequencing of mitochondrial ribosomal fractions, molecular analyses of polyadenylation and translation PLoS genetics High 26247782
2003 LRP130/LRPPRC is directly bound in vivo to mitochondrial polyadenylated RNAs and to nuclear mRNAs also associated with hnRNP A1. In vitro, LRP130 binds preferentially to polypyrimidines, with RNA-binding activity mapping to a C-terminal domain containing only 2 of 11 predicted PPR motifs — a novel non-canonical RNA-binding domain. The majority of LRP130 is localized within mitochondria. In vivo RNA crosslinking/immunoprecipitation, in vitro RNA-binding assays, subcellular fractionation, domain mapping Molecular and cellular biology High 12832482
2013 LRPPRC does not activate mitochondrial transcription. Size exclusion chromatography and immunoprecipitation in human cell lines and mice found no interaction between LRPPRC and the mitochondrial RNA polymerase POLRMT. Addition of purified LRPPRC to a recombinant in vitro transcription system did not activate mtDNA transcription. Variation of LRPPRC levels in vivo affected unprocessed precursor transcript levels but not steady-state mRNA levels or de novo transcription. Size exclusion chromatography, co-immunoprecipitation, in vitro transcription reconstitution, BAC transgenic mice, heterozygous knockout mice The Journal of biological chemistry High 23599432
2010 LRPPRC is exclusively localized to the mitochondrial matrix in mammalian cells; a single protein isoform exists, its mitochondrial targeting sequence is cleaved upon import, and orthologs are restricted to metazoans with conserved mitochondrial targeting signals. Subcellular fractionation, bioinformatic analysis of targeting sequences, direct protein localization experiments in mammalian cells Biochemical and biophysical research communications Medium 20633537
2006 LRP130/LRPPRC is a component of the PGC-1α transcriptional coactivator complex and is required for PGC-1α-dependent expression of gluconeogenic genes PEPCK and G6P, as well as certain mitochondrial genes. Adenoviral RNAi knockdown of LRP130 in fasted mice blocked PEPCK and G6P induction and blunted hepatic glucose output. Co-purification/mass spectrometry identification of PGC-1α complex components, adenoviral RNAi in mice, gene expression analysis Genes & development High 17050673
2011 LRP130/LRPPRC complexes with the mitochondrial RNA polymerase (POLRMT) to activate mitochondrial transcription (as assessed by convergent genetic and biochemical approaches), which is associated with increased OXPHOS activity, increased supercomplex formation, denser cristae, and increased hepatic β-fatty acid oxidation. Co-immunoprecipitation, genetic overexpression, biochemical OXPHOS activity assays, fatty acid oxidation assay with 14C-palmitate The Journal of biological chemistry Low 21971050
2014 Loss of LRPPRC in conditional knockout mouse hearts causes ATP synthase deficiency rather than solely COX deficiency; inactive subassembled ATP synthase complexes accumulate, causing mitochondrial hyperpolarization and increased reactive oxygen species production. Conditional Lrpprc knockout mouse hearts, OXPHOS complex activity assays, mitochondrial membrane potential measurement, ROS measurement Human molecular genetics High 24399447
2004 LRPPRC protein levels are reduced to <30% of control in fibroblast and liver mitochondria from LSFC patients carrying the A354V mutation. Reduced LRPPRC results in decreased COX I and COX III mRNA levels and specifically reduced translation of COX I. Import of the mutant A354V LRPPRC into rat liver mitochondria is slower than wild-type. Northern blot for mitochondrial mRNAs, [35S]methionine mitochondrial translation labeling, mitochondrial import assay, immunofluorescence The Biochemical journal Medium 15139850
2012 LRPPRC requires its first 19 PPR motifs for full binding to COX I mRNA; a specific segment of COX I mRNA encoded by mouse mtDNA nucleotides 5961–6020 was identified as the binding target. Homozygous LRPPRC C-terminus truncation causes embryonic lethality and major decrease in COX activity in mouse embryonic fibroblasts. Recombinant protein expression with PPR domain truncations, in vitro RNA-binding assay, gene-trap mouse model, COX activity assay The Biochemical journal Medium 21880015
2013 Reducing mma-1/LRPPRC function in C. elegans and mammalian cells causes mitochondrial hyperfusion as a compensatory response to decreased complex IV activity. Preventing mitochondrial hyperfusion in mma-1 animals causes larval arrest and embryonic lethality. Prolonged LRPPRC knockdown in mammalian cells leads to subsequent mitochondrial fragmentation and decreased ATP. C. elegans mma-1 mutants and mammalian LRPPRC knockdown, live-cell mitochondrial morphology imaging, genetic epistasis, ATP measurement Proceedings of the National Academy of Sciences of the United States of America High 23878239
2013 LRPPRC interacts with Beclin 1 and Bcl-2 to form a ternary complex that maintains Bcl-2 stability. Suppression of LRPPRC reduces mitochondrial membrane potential and Bcl-2 levels, releasing Beclin 1 to activate the PI3K/Akt/mTOR autophagy pathway, thereby initiating basal autophagy and mitochondrial turnover. Co-immunoprecipitation, GFP-LC3 puncta assay, LC3-II/p62 western blot, siRNA knockdown in multiple cell lines, mitochondrial membrane potential assay The Biochemical journal Medium 23822101
2014 Under mitophagy stress, Parkin translocates to mitochondria and binds to exposed LRPPRC on the outer mitochondrial membrane. LRPPRC maintains Parkin stability (Parkin mono-ubiquitinates Bcl-2 to increase its stability and inhibit autophagy). LRPPRC and Parkin together facilitate engulfment of mitochondria into autophagosomes. Co-immunoprecipitation, subcellular fractionation, CCCP-induced mitophagy, western blot for Parkin/Bcl-2/LC3 markers PloS one Low 24722279
2015 LRPPRC knockdown in mammalian cells causes an imbalance between mitochondria-encoded and nuclear-encoded complex IV subunits that triggers the mitochondrial unfolded protein response (UPRmt). Inactivation of LRPPRC homolog mma-1 in C. elegans also induces UPRmt, demonstrating evolutionary conservation. Mitochondrial hyperfusion and UPRmt are coordinated but mediated by genetically distinct pathways. siRNA knockdown in mammalian cells, C. elegans mma-1 mutants, UPRmt reporter assays, genetic epistasis Aging Medium 26412102
2004 LRP130/LRPPRC binds to a 12 bp invMED1 cis-activating element in the MDR1 gene promoter as a nuclear factor, and its binding intensity correlates with MDR1 expression level. LRP130 regulates transcriptional activity of both MDR1 and MVP gene promoters, as demonstrated by siRNA and transcriptional decoys. Electrophoretic mobility shift assay, siRNA knockdown, transcriptional decoys, luciferase reporter assay, chromatin immunoprecipitation Nucleic acids research Medium 15272088
2008 LRP130 is a binding partner of PGC-1α in brown adipocytes, is preferentially enriched in brown fat, and is required for PGC-1α-dependent expression of UCP1 and other brown fat genes. Brown fat cells deficient for LRP130 exhibit reduced proton leak due to attenuated UCP1 expression. Co-immunoprecipitation, LRP130 knockdown in brown adipocytes, oxygen consumption assay, gene expression analysis The Journal of biological chemistry Medium 18728005
2018 LRPPRC acts as a negative regulator of MAVS-mediated antiviral signaling by interacting with MAVS and inhibiting its association with TRAF3 and TRAF6. LRPPRC knockdown results in inhibition of HCV infection associated with increased IFN response activation. The HCV NS5A protein exploits LRPPRC to interfere with MAVS activity in a LRPPRC-dependent manner. Co-immunoprecipitation (LRPPRC-MAVS, MAVS-TRAF3, MAVS-TRAF6), siRNA knockdown, HCV infection assay, IFN response measurement Hepatology (Baltimore, Md.) Medium 30070380
2024 SIRT3 binds to and deacetylates LRPPRC, and this deacetylation modulates mitochondrial function (oxidative phosphorylation and oxidative stress) and cellular senescence. LRPPRC in turn regulates senescence by modulating OXPHOS and oxidative stress. Co-immunoprecipitation, western blot with acetylation antibodies, SIRT3 overexpression/knockdown, in vitro and in vivo senescence assays Free radical biology & medicine Low 39557134
2022 LRPPRC specifically binds to MDR1 mRNA and increases its stability and protein expression. P53-induced miR-34a suppresses LRPPRC expression; when P53 is mutated, accumulated LRPPRC stabilizes MDR1 mRNA, promoting chemoresistance. Gossypol-acetic acid (GAA) induces degradation of LRPPRC protein and reduces chemoresistance. RNA immunoprecipitation (RIP), mRNA stability assay, miR-34a reporter assay, GAA treatment with western blot and proliferation assays, in vivo xenograft Cell death and differentiation Medium 35484333
2023 LRPPRC promotes the synthesis of OXPHOS subunits by binding to RNAs encoded by mitochondrial DNA. Gossypol acetic acid (GAA) binds directly to LRPPRC and induces its rapid degradation in a ubiquitin-independent manner, suppressing OXPHOS complex synthesis. RNA binding pulldown, LC-MS target identification, GAA direct binding assay, ubiquitination assay, OXPHOS subunit expression analysis, xenograft Journal of translational medicine Medium 37496051
2023 LRPPRC promotes CDK4/6 inhibitor resistance in lung cancer by binding to CDK6 mRNA and increasing CDK6 mRNA stability and protein expression. CDK6 downstream effector E2F1 binds the LRPPRC promoter, forming a feedback loop; this LRPPRC-CDK6 loop facilitates G1/S transition, OXPHOS, and cancer stem cell generation. RNA immunoprecipitation (RIP) for LRPPRC-CDK6 mRNA, mRNA stability assay, promoter binding (ChIP), CDK4/6 inhibitor resistance assays in vitro and in vivo Nature communications Medium 37452037
2021 SNHG17 lncRNA physically interacts with the 1035–1369 aa domain of LRPPRC protein; this interaction is required for LRPPRC to inhibit c-Myc ubiquitination and promote c-Myc stability, G1/S transition, and cell proliferation. RNA pull-down, co-immunoprecipitation, c-Myc ubiquitination assay, domain mapping, rescue experiments with LRPPRC/SNHG17 silencing Cell death & disease Low 34671012
2024 LRPPRC acts as an m6A reader that binds m6A-modified PD-L1 mRNA and stabilizes it posttranscriptionally in an m6A-dependent manner, increasing PD-L1 expression. LRPPRC loss downregulates PD-L1 and its m6A level in HCC cells and improves anti-tumor immunity in murine models. RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP-qPCR), RNA stability assay, LRPPRC knockout in HCC cells and mouse models Frontiers in immunology Low 37063837
2024 LRPPRC recognizes m6A modification sites on LDHA mRNA and enhances LDHA mRNA stability, promoting glycolysis in triple-negative breast cancer. LRPPRC knockdown reduces glycolysis and increases glutaminolysis; combined LRPPRC knockdown plus glutaminase inhibition induces synthetic lethality. MeRIP-sequencing, RNA immunoprecipitation (RIP), RNA pull-down, RNA stability assay, Seahorse metabolic assay, patient-derived xenografts and organoids Clinical and translational medicine Medium 38372449
2024 The LRPPRC-SLIRP complex is required for maintaining normal complex I levels in vivo; disruption of complex formation by knock-in mutations causes partial LRPPRC degradation and disappearance of SLIRP. The complex coordinates mitochondrial translation in a tissue-specific manner, and introducing an additive mtDNA mutation (m.C5024T tRNA-Ala) into Slirp knockout mice causes embryonic lethality through additive translation defects. Knock-in mice with LRPPRC-SLIRP interface mutations, SLIRP knockout mice, mitochondrial translation assays, complex I activity measurement, genetic epistasis with mtDNA mutation Nucleic acids research High 39087558
2025 USP44 recruits and stabilizes E3 ubiquitin ligase STUB1 by removing its K48-linked polyubiquitin chains at Lys30. STUB1 in turn promotes K48-linked polyubiquitination of LRPPRC at Lys453, leading to LRPPRC protein degradation and accumulation of mitochondrial ROS, facilitating apoptosis and cisplatin sensitivity in neuroblastoma. Co-immunoprecipitation, ubiquitination site mapping (K453), mass spectrometry, overexpression and knockdown with rescue experiments, in vivo tumor models Neuro-oncology Medium 39215663
2022 PSMD14 deubiquitinase directly interacts with LRPPRC and inhibits its ubiquitination, thereby stabilizing LRPPRC protein. This LRPPRC stabilization inhibits autophagy through the LRPPRC/Beclin1-Bcl-2/SQSTM1 signaling pathway, promoting ovarian cancer progression. Co-immunoprecipitation, ubiquitination assay, PSMD14 knockdown/overexpression, in vivo tumor growth and metastasis assay Biochimica et biophysica acta. Molecular basis of disease Low 36328147
2023 In Drosophila, loss of lrpprc2 activates the PINK1-Park (Parkin) pathway, which regulates mitochondrial dynamics by inducing degradation of the mitochondrial fusion protein Mitofusin/Marf, rather than canonical mitophagy. Bendless (a K63-linked E2 conjugase) is required for PINK1 stability and for PINK1-Park-mediated Marf degradation; loss of Bendless in lrpprc2 mutants causes photoreceptor degeneration. Unbiased genetic screen in Drosophila, lrpprc2 mutant analysis, epistasis experiments with PINK1/Park/Bendless, Mitofusin/Marf protein level assays PLoS genetics Medium 37098042
2020 LRP130/LRPPRC acts as a scaffold component of a transcriptional repressor complex with PGC1α; the lncRNA GUARDIN stabilizes LRP130/PGC1α heterodimers and their occupancy at the FOXO4 promoter. Silencing LRP130 or PGC1α leads to increased FOXO4 expression, upregulation of p21, and cellular senescence. Co-immunoprecipitation of LRP130-PGC1α complex, chromatin immunoprecipitation at FOXO4 promoter, siRNA knockdown, senescence assays EMBO reports Low 32149459

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. The EMBO journal 286 22045337
2012 LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria. Nucleic acids research 162 22661577
2004 The role of the LRPPRC (leucine-rich pentatricopeptide repeat cassette) gene in cytochrome oxidase assembly: mutation causes lowered levels of COX (cytochrome c oxidase) I and COX III mRNA. The Biochemical journal 142 15139850
2003 LRP130, a pentatricopeptide motif protein with a noncanonical RNA-binding domain, is bound in vivo to mitochondrial and nuclear RNAs. Molecular and cellular biology 132 12832482
2019 LRPPRC: A Multifunctional Protein Involved in Energy Metabolism and Human Disease. Frontiers in physiology 105 31178748
2017 LRPPRC-mediated folding of the mitochondrial transcriptome. Nature communications 103 29146908
2014 Loss of LRPPRC causes ATP synthase deficiency. Human molecular genetics 97 24399447
2015 LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population. Brain : a journal of neurology 87 26510951
2006 Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex. Genes & development 86 17050673
2015 SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation. PLoS genetics 83 26247782
2011 LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency. Journal of medical genetics 79 21266382
2010 Mitochondrial and nuclear genomic responses to loss of LRPPRC expression. The Journal of biological chemistry 74 20220140
2022 Targeting the miR-34a/LRPPRC/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer. Cell death and differentiation 72 35484333
2013 Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion. Proceedings of the National Academy of Sciences of the United States of America 68 23878239
2002 Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggests roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic shuttling, and chromosome activity. Genomics 68 11827465
2013 Mitochondrion-associated protein LRPPRC suppresses the initiation of basal levels of autophagy via enhancing Bcl-2 stability. The Biochemical journal 57 23822101
2012 Role of leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) for anti-apoptosis and tumourigenesis in cancers. European journal of cancer (Oxford, England : 1990) 54 22326293
2014 Tissue-specific responses to the LRPPRC founder mutation in French Canadian Leigh Syndrome. Human molecular genetics 50 25214534
2011 LRP130 protein remodels mitochondria and stimulates fatty acid oxidation. The Journal of biological chemistry 50 21971050
2008 Modulation of PGC-1 coactivator pathways in brown fat differentiation through LRP130. The Journal of biological chemistry 49 18728005
2016 SLIRP stabilizes LRPPRC via an RRM-PPR protein interface. Nucleic acids research 47 27353330
2021 LncRNA SNHG17 interacts with LRPPRC to stabilize c-Myc protein and promote G1/S transition and cell proliferation. Cell death & disease 45 34671012
2010 LRPPRC is a mitochondrial matrix protein that is conserved in metazoans. Biochemical and biophysical research communications 45 20633537
2017 Loss of hepatic LRPPRC alters mitochondrial bioenergetics, regulation of permeability transition and trans-membrane ROS diffusion. Human molecular genetics 43 28575497
2014 Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin. PloS one 43 24722279
2023 LRPPRC facilitates tumor progression and immune evasion through upregulation of m6A modification of PD-L1 mRNA in hepatocellular carcinoma. Frontiers in immunology 42 37063837
2013 The significance of LRPPRC overexpression in gastric cancer. Medical oncology (Northwood, London, England) 40 24375316
2021 LRPPRC regulates redox homeostasis via the circANKHD1/FOXM1 axis to enhance bladder urothelial carcinoma tumorigenesis. Redox biology 38 34864630
2020 LRPPRC sustains Yap-P27-mediated cell ploidy and P62-HDAC6-mediated autophagy maturation and suppresses genome instability and hepatocellular carcinomas. Oncogene 38 32203162
2018 Negative Regulation of Mitochondrial Antiviral Signaling Protein-Mediated Antiviral Signaling by the Mitochondrial Protein LRPPRC During Hepatitis C Virus Infection. Hepatology (Baltimore, Md.) 38 30070380
2004 LRP130, a single-stranded DNA/RNA-binding protein, localizes at the outer nuclear and endoplasmic reticulum membrane, and interacts with mRNA in vivo. Biochemical and biophysical research communications 37 15081402
2002 LRP130, a protein containing nine pentatricopeptide repeat motifs, interacts with a single-stranded cytosine-rich sequence of mouse hypervariable minisatellite Pc-1. European journal of biochemistry 37 12071956
2023 The RNA-binding protein LRPPRC promotes resistance to CDK4/6 inhibition in lung cancer. Nature communications 35 37452037
2024 Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome. Nature structural & molecular biology 34 39134711
2020 Alzheimer's and Parkinson's brain tissues have reduced expression of genes for mtDNA OXPHOS Proteins, mitobiogenesis regulator PGC-1α protein and mtRNA stabilizing protein LRPPRC (LRP130). Mitochondrion 34 32497722
2012 LRPPRC mutation suppresses cytochrome oxidase activity by altering mitochondrial RNA transcript stability in a mouse model. The Biochemical journal 34 21880015
2016 The effect of acute and chronic sprint-interval training on LRP130, SIRT3, and PGC-1α expression in human skeletal muscle. Physiological reports 33 27604398
2021 LRPPRC regulates metastasis and glycolysis by modulating autophagy and the ROS/HIF1-α pathway in retinoblastoma. Molecular therapy oncolytics 30 34589577
2020 Novel LRPPRC compound heterozygous mutation in a child with early-onset Leigh syndrome French-Canadian type: case report of an Italian patient. Italian journal of pediatrics 29 32972427
2004 New invMED1 element cis-activates human multidrug-related MDR1 and MVP genes, involving the LRP130 protein. Nucleic acids research 28 15272088
2016 Increased Hepatic Fatty Acids Uptake and Oxidation by LRPPRC-Driven Oxidative Phosphorylation Reduces Blood Lipid Levels. Frontiers in physiology 27 27462273
2013 The leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) does not activate transcription in mammalian mitochondria. The Journal of biological chemistry 27 23599432
2015 The loss of LRPPRC function induces the mitochondrial unfolded protein response. Aging 25 26412102
2023 A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC-OXPHOS axis. Journal of translational medicine 24 37496051
2022 Deubiquitylase PSMD14 inhibits autophagy to promote ovarian cancer progression via stabilization of LRPPRC. Biochimica et biophysica acta. Molecular basis of disease 24 36328147
2024 LRPPRC promotes glycolysis by stabilising LDHA mRNA and its knockdown plus glutamine inhibitor induces synthetic lethality via m6 A modification in triple-negative breast cancer. Clinical and translational medicine 23 38372449
2015 The viral restriction factor tetherin prevents leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) from association with beclin 1 and B-cell CLL/lymphoma 2 (Bcl-2) and enhances autophagy and mitophagy. The Journal of biological chemistry 23 25631043
2024 SIRT3 alleviates mitochondrial dysfunction and senescence in diabetes-associated periodontitis by deacetylating LRPPRC. Free radical biology & medicine 21 39557134
2022 A/(H1N1) pdm09 NS1 promotes viral replication by enhancing autophagy through hijacking the IAV negative regulatory factor LRPPRC. Autophagy 21 36300799
2020 LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-FOXO4-p21-dependent signaling axis. EMBO reports 20 32149459
2012 Knockdown of the cellular protein LRPPRC attenuates HIV-1 infection. PloS one 20 22808186
2012 A comparative proteomic study identified LRPPRC and MCM7 as putative actors in imatinib mesylate cross-resistance in Lucena cell line. Proteome science 19 22458888
2024 LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation. Nucleic acids research 18 39087558
2017 Immunohistochemical expression analysis of leucine-rich PPR-motif-containing protein (LRPPRC), a candidate colorectal cancer biomarker identified by shotgun proteomics using iTRAQ. Clinica chimica acta; international journal of clinical chemistry 17 28622966
2015 Aerobic Exercise Recovers Disuse-induced Atrophy Through the Stimulus of the LRP130/PGC-1α Complex in Aged Rats. The journals of gerontology. Series A, Biological sciences and medical sciences 16 25991827
2014 ABCB1 regulation through LRPPRC is influenced by the methylation status of the GC -100 box in its promoter. Epigenetics 16 25089713
2021 LRPPRC contributes to the cisplatin resistance of lung cancer cells by regulating MDR1 expression. Oncology reports 15 33649818
2025 LRPPRC confers enhanced oxidative phosphorylation metabolism in triple-negative breast cancer and represents a therapeutic target. Journal of translational medicine 14 40133967
2017 Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French-Canadian Type Outside of Québec. Child neurology open 14 29152527
2024 Targeting leucine-rich PPR motif-containing protein/LRPPRC by 5,7,4'-trimethoxyflavone suppresses esophageal squamous cell carcinoma progression. International journal of biological macromolecules 13 38697422
2020 Poly (A) tail length of human mitochondrial mRNAs is tissue-specific and a mutation in LRPPRC results in transcript-specific patterns of deadenylation. Molecular genetics and metabolism reports 13 33312877
2019 mTORC1 is required for expression of LRPPRC and cytochrome-c oxidase but not HIF-1α in Leigh syndrome French Canadian type patient fibroblasts. American journal of physiology. Cell physiology 13 30995105
2023 LRPPRC regulates malignant behaviors, protects mitochondrial homeostasis, mitochondrial function in osteosarcoma and derived cancer stem-like cells. BMC cancer 11 37789316
2014 Downregulation of LRPPRC induces apoptosis in prostate cancer cells through the mitochondria-mediated pathway. Cancer biotherapy & radiopharmaceuticals 11 25379610
2025 The deubiquitinase USP44 enhances cisplatin chemosensitivity through stabilizing STUB1 to promote LRPPRC degradation in neuroblastoma. Neuro-oncology 10 39215663
2025 Demethylzeylasteral inhibits oxidative phosphorylation complex biogenesis by targeting LRPPRC in lung cancer. Journal of Cancer 10 39744573
2024 Comprehensive review on leucine-rich pentatricopeptide repeat-containing protein (LRPPRC, PPR protein): A burgeoning target for cancer therapy. International journal of biological macromolecules 10 39476900
2020 Propofol induces mitochondrial-associated protein LRPPRC and protects mitochondria against hypoxia in cardiac cells. PloS one 10 32898195
2022 LRPPRC inhibits autophagy and promotes foam cell formation in atherosclerosis. The FEBS journal 9 35792704
2021 Adaptive optimization of the OXPHOS assembly line partially compensates lrpprc-dependent mitochondrial translation defects in mice. Communications biology 9 34413467
2024 An LRPPRC-HAPSTR1-PSMD14 interaction regulates tumor progression in ovarian cancer. Aging 7 38643468
2024 Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction. World journal of stem cells 7 38690512
2024 hsa_circ_0020093 suppresses ovarian cancer progression by modulating LRPPRC activity and miR-107/LATS2 signaling. Biology direct 7 39164777
2025 N6-Methyladenosine (m6A) Reader LRPPRC-Mediated CXCL11 Induces Cell Inflammation to Drive Breast Cancer Cell Malignancy. Critical reviews in immunology 6 39612279
2021 Pseudorabies virus UL16 protein influences the inhibition of LRPPRC for the viral proliferation. Veterinary microbiology 6 34986434
2020 Fiber-specific and whole-muscle LRP130 expression in rested, exercised, and fasted human skeletal muscle. Pflugers Archiv : European journal of physiology 6 32065259
2020 Mitochondria-associated protein LRPPRC exerts cardioprotective effects against doxorubicin-induced toxicity, potentially via inhibition of ROS accumulation. Experimental and therapeutic medicine 6 32855734
2024 Design, synthesis, and biological evaluation of novel 5,7,4'-trimethoxyflavone sulfonamide-based derivatives as highly potent inhibitors of LRPPRC/STAT3/CDK1. Bioorganic chemistry 5 39395319
2024 METTL3-mediated SMPDL3A promotes cell growth, metastasis and immune process of hepatocellular carcinoma by regulating LRPPRC. Cellular signalling 5 39631618
2023 Bendless is essential for PINK1-Park mediated Mitofusin degradation under mitochondrial stress caused by loss of LRPPRC. PLoS genetics 5 37098042
2023 A novel homozygous splice donor variant in the LRPPRC gene causing Leigh syndrome with epilepsy, a French-Canadian disorder in a Saudi family: case report. Frontiers in pediatrics 3 38046674
2025 Landscape analysis of m6A modification regulators reveals LRPPRC as a key modulator in tubule cells for DKD: a multi-omics study. Frontiers in pharmacology 2 40255566
2025 The Biological Role of LRPPRC in Human Cancers. Cancer control : journal of the Moffitt Cancer Center 2 40587247
2025 Identification and validation of the m6A-binding protein LRPPRC to promote tumorigenesis in multiple myeloma. Hematology (Amsterdam, Netherlands) 2 40611540
2025 Leucyl-tRNA synthetase promotes malignant progression in diffuse large B-cell lymphoma by regulating glycolysis via the LRPPRC/HIF-1α/HK2 axis. Human cell 2 40775462
2025 LRPPRC promotes the progression of colorectal cancer via HIF-1ꭤ/VEGF-meditated angiogenesis. Pathology, research and practice 2 40957301
2024 Human induced pluripotent stem cells (hiPSCs) derived cells reflect tissue specificity found in patients with Leigh syndrome French Canadian variant (LSFC). Frontiers in genetics 2 38706791
2026 Therapeutic targeting LRPPRC-mediated OXPHOS synthesis for cancer intervention. Expert opinion on therapeutic targets 1 41491301
2025 The Identification of a Key Regulator of Mitochondrial Metabolism, the LRPPRC Protein, as a Novel Therapeutic Target in SDHA-Overexpressing Ovarian Tumors. Cancers 1 40563592
2025 LRPPRC-Driven Oxidative Phosphorylation Is Associated with Elesclomol-Induced Cuproptosis in Ovarian Cancer. International journal of molecular sciences 1 41516324
2019 [Knock-down of leucine-rich pentatricopeptide repeat containing(LRPPRC) promotes apoptosis of hormone resistant prostate cancer cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 31223111
2026 Design, synthesis, and antitumor activity of novel Flavokawain A derivatives by suppressing LRPPRC-YBX1-RPN1 cascade. Bioorganic chemistry 0 41529605
2026 PRKAB2 as a tumor suppressor in renal cell carcinoma: inhibiting mitophagy via the LRPPRC-PRKN/parkin interaction and cardiolipin biosynthesis. Autophagy 0 41612594
2026 Synergistic Anti-Tumor Activity of LRPPRC Inhibition and Dasatinib Through Dual Oxidative Phosphorylation Disruption. Pharmaceuticals (Basel, Switzerland) 0 41901318
2026 Targeting LRPPRC lactylation disrupts metabolic-immune crosstalk and restores antitumor immunity in hepatocellular carcinoma. Translational cancer research 0 41969495
2025 Programmable Loading of a Multivalent LRPPRC Aptamer onto a Rectangular DNA Tile Inhibits the Proliferation of Lung Adenocarcinoma Cells. ACS applied materials & interfaces 0 40223205
2025 Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC)-stabilized lncRNA small nucleolar RNA host gene 15 (Snhg15) modulates hematopoietic injury induced by γ-ray irradiation via m6A modification. Molecular biomedicine 0 40555877
2025 Disruption of Lrpprc affects B cell development and proliferation in a mouse model of Leigh Syndrome French Canadian type. Journal of rare diseases (Berlin, Germany) 0 40607235
2025 Mitochondria-located circRCP regulates redox homeostasis via stabilizing LRPPRC/SLIRP complex to promote bladder urothelial carcinoma tumorigenesis. Cancer letters 0 41274398
2025 Two Siblings with LRPPRC Mutation: Mitochondrial Complex IV Deficiency: Case Report. Molecular syndromology 0 42232680

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