ArticleScientific reports2020
Calcium mishandling in absence of primary mitochondrial dysfunction drives cellular pathology in Wolfram Syndrome.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Molecular and Inflammatory Etiologies of β-Cell Dysfunction in Type 1 Diabetes.Physiology (Bethesda, Md.) · 2025Review
- Reciprocal rescue of Wolfram syndrome by two causative genes.EMBO reports · 2025Article
- Topology ofPediatric diabetes · 2025Article
- A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome.Diabetologia · 2025Article
- Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.International journal of molecular sciences · 2024Review
- Molecular recording of calcium signals via calcium-dependent proximity labeling.Nature chemical biology · 2024Article
- Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Review
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- Skeletal Health in Patients With Mitochondrial Diabetes: Case Series and Review of Literature.JBMR plus · 2023Article
- Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome.Stem cell reports · 2023Article
- Article
- Evaluation of the Oral Bacterial Genome and Metabolites in Patients with Wolfram Syndrome.International journal of molecular sciences · 2023Article
- Article
- Case Report: A novel mutation inFrontiers in genetics · 2023Article
- Complex clinical manifestations and new insights in RNA sequencing of children with diabetes andFrontiers in endocrinology · 2023Article
- Multidimensional analysis and therapeutic development using patient iPSC-derived disease models of Wolfram syndrome.JCI insight · 2022Article
- Wolframin deficiency is accompanied with metabolic inflexibility in rat striated muscles.Biochemistry and biophysics reports · 2022Article
- Multiomic analysis on human cell model of wolfram syndrome reveals changes in mitochondrial morphology and function.Cell communication and signaling : CCS · 2021Article
- The Expression of RAAS Key Receptors,Genes · 2021Article
- A mutant wfs1 zebrafish model of Wolfram syndrome manifesting visual dysfunction and developmental delay.Scientific reports · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wolfram syndrome (WS) is a recessive multisystem disorder defined by the association of diabetes mellitus and optic atrophy, reminiscent of mitochondrial diseases. The role played by mitochondria remains elusive, with contradictory results on the occurrence of mitochondrial dysfunction. We evaluated 13 recessive WS patients by deep clinical phenotyping, including optical coherence tomography (OCT), serum lactic acid at rest and after standardized exercise, brain Magnetic Resonance Imaging, and brain and muscle Magnetic Resonance Spectroscopy (MRS). Finally, we investigated mitochondrial bioenergetics, network morphology, and calcium handling in patient-derived fibroblasts. Our results do not support a primary mitochondrial dysfunction in WS patients, as suggested by MRS studies, OCT pattern of retinal nerve fiber layer loss, and, in fibroblasts, by mitochondrial bioenergetics and network morphology results. However, we clearly found calcium mishandling between endoplasmic reticulum (ER) and mitochondria, which, under specific metabolic conditions of increased energy requirements and in selected tissue or cell types, may turn into a secondary mitochondrial dysfunction. Critically, we showed that Wolframin (WFS1) protein is enriched at mitochondrial-associated ER membranes and that in patient-derived fibroblasts WFS1 protein is completely absent. These findings support a loss-of-function pathogenic mechanism for missense mutations in WFS1, ultimately leading to defective calcium influx within mitochondria.
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