ArticleHuman molecular genetics2015
Tissue-specific responses to the LRPPRC founder mutation in French Canadian Leigh Syndrome.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- LRPPRC: A Multifunctional Protein Involved in Energy Metabolism and Human Disease.Frontiers in physiology · 2019Pooled it
- SLIRP differentially modulates RNA binding of pathogenic LRPPRC variants.NAR molecular medicine · 2026Article
- Two Siblings withMolecular syndromology · 2026Article
- Hyperglycemia impairs cognitive function by inducing mitochondrial damage through lactylation of LRPPRC at K223.EMBO molecular medicine · 2026Article
- 4,5-dihydroxyhexanoic acid is a robust circulating and urine marker of mitochondrial disease and its severity.bioRxiv : the preprint server for biology · 2026Article
- Largely Distinct Post-Translational Modifications Differentiate Skeletal Muscle Wasting Caused by Cancer, Dexamethasone and Aging.Journal of cachexia, sarcopenia and muscle · 2026Article
- An RNA transmethylation pathway governs kidney nephrogenic potential.Nature communications · 2025Article
- Multi-trait Genome-Wide Analysis Identified 20 Novel Loci for Sarcopenia-Related Traits in UK Biobank.Calcified tissue international · 2025Article
- Disruption ofJournal of rare diseases (Berlin, Germany) · 2025Article
- Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome.Nature structural & molecular biology · 2024Article
- The human mitochondrial translation factor TACO1 alleviates mitoribosome stalling at polyproline stretches.Nucleic acids research · 2024Article
- Mitochondrial protein synthesis quality control.Human molecular genetics · 2024Review
- Illuminating mitochondrial translation through mouse models.Human molecular genetics · 2024Review
- A genetic mouse model of lean-NAFLD unveils sexual dimorphism in the liver-heart axis.Communications biology · 2024Article
- Human induced pluripotent stem cells (hiPSCs) derived cells reflect tissue specificity found in patients with Leigh syndrome French Canadian variant (LSFC).Frontiers in genetics · 2024Article
- Mitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus.Developmental cell · 2023Article
- High-throughput sequencing analysis of nuclear-encoded mitochondrial genes reveals a genetic signature of human longevity.GeroScience · 2023Article
- A novel homozygous splice donor variant in theFrontiers in pediatrics · 2023Article
- Article
- Expression signature of the Leigh syndrome French-Canadian type.Molecular genetics and metabolism reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
French Canadian Leigh Syndrome (LSFC) is an early-onset, progressive neurodegenerative disorder with a distinct pattern of tissue involvement. Most cases are caused by a founder missense mutation in LRPPRC. LRPPRC forms a ribonucleoprotein complex with SLIRP, another RNA-binding protein, and this stabilizes polyadenylated mitochondrial mRNAs. LSFC fibroblasts have reduced levels of LRPPRC and a specific complex IV assembly defect; however, further depletion of mutant LRPPRC results in a complete failure to assemble a functional oxidative phosphorylation system, suggesting that LRPPRC levels determine the nature of the biochemical phenotype. We tested this hypothesis in cultured muscle cells and tissues from LSFC patients. LRPPRC levels were reduced in LSFC muscle cells, resulting in combined complex I and IV deficiencies. A similar combined deficiency was observed in skeletal muscle. Complex IV was only moderately reduced in LSFC heart, but was almost undetectable in liver. Both of these tissues showed elevated levels of complexes I and III. Despite the marked biochemical differences, the steady-state levels of LRPPRC and mitochondrial mRNAs were extremely low, LRPPRC was largely detergent-insoluble, and SLIRP was undetectable in all LSFC tissues. The level of the LRPPRC/SLIRP complex appeared much reduced in control tissues by the first dimension blue-native polyacrylamide gel electrophoresis (BN-PAGE) analysis compared with fibroblasts, and even by second dimension analysis it was virtually undetectable in control heart. These results point to tissue-specific pathways for the post-transcriptional handling of mitochondrial mRNAs and suggest that the biochemical defects in LSFC reflect the differential ability of tissues to adapt to the mutation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.