ArticleNature communications2023
Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07474779 (From Genes to Virtual Brain), which is not on this map. Cited by 56 papers.
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.
From Genes to Virtual Brain: Defining the Pathogenic Mechanisms Promoting Alfa-synuclein Seeding and Spreading in Parkinson's Disease.
Who cites it
56 citing papers in PubMed, 78 citations in OpenAlex.
- Engineering functional ventral midbrain dopaminergic neurons in human organoids through WNT modulation and bioreactor culture.Molecular psychiatry · 2026Article
- Rare-Variant Burden across Lysosomal Genes Implicates Sialylation and Ganglioside Metabolism in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Review
- The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.Nature neuroscience · 2026Article
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Targeting lysosomal pH restores mitochondrial quality control in GBA1-mutant Parkinson's disease.Translational neurodegeneration · 2026Article
- Article
- The c-Abl-RIPK3 Axis Drives Mitochondrial Dysfunction and Impaired Mitophagy in Gaucher Disease Models.Antioxidants (Basel, Switzerland) · 2026Article
- GBA1 F213I mutation increases the expression of LCN2 promoting neurodegeneration.Cell death and differentiation · 2026Article
- The dual impact of GBA1 in disease: from germline mutations in neurological disorders to alterations in cancer.Cell death discovery · 2026Review
- Behavioral screening defines the molecular Parkinsonism-related subgroups in Drosophila.Nature communications · 2026Article
- Polymeric nanoparticle-mediated GBA1 gene therapy is neuroprotective in a preclinical model of Parkinson's disease.Drug delivery and translational research · 2026Article
- Rare-variant burden across lysosomal genes implicates sialylation and ganglioside metabolism in Parkinson's disease.medRxiv : the preprint server for health sciences · 2026Article
- Multi-omics insights into GBA1-associated Parkinson's disease: interplay of genomics, transcriptomics, proteomics, and lipidomics.Molecular neurodegeneration · 2026Review
- Constraint-based modelling of metabolic dysregulation in Gaucher disease: mitochondrial dysfunction and disrupted cholesterol homeostasis.Orphanet journal of rare diseases · 2026Article
- Current and emerging drugs for Parkinson's disease: mechanisms, clinical evidence, and future directions.Frontiers in pharmacology · 2026Review
- Oleuropein Aglycone, an Olive Polyphenol, Influences Alpha-Synuclein Aggregation and Exerts Neuroprotective Effects in Different Parkinson's Disease Models.Molecular neurobiology · 2025Article
- Metabolic reprogramming and altered ATP content impair neuroprotective functions of microglia in β-glucocerebrosidase deficiency models.Journal of neuroinflammation · 2025Article
- Decoding nuclear-encoded mitochondrial genes in major depressive disorder: A multi-omics perspective.Psychological medicine · 2025Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in GBA1, the gene encoding the lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher's disease, are the most frequent genetic risk factor for Parkinson's disease (PD). Here, we employ global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from the cytosol into the mitochondria via recognition of internal mitochondrial targeting sequence-like signals. In mitochondria, GCase promotes the maintenance of mitochondrial complex I (CI) integrity and function. Furthermore, GCase interacts with the mitochondrial quality control proteins HSP60 and LONP1. Disease-associated mutations impair CI stability and function and enhance the interaction with the mitochondrial quality control machinery. These findings reveal a mitochondrial role of GCase and suggest that defective CI activity and energy metabolism may drive the pathogenesis of GCase-linked neurodegeneration.
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.