ArticleThe Journal of clinical investigation2023
RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Pathomechanism of Fever-Induced Liver Failure in NBAS Deficiency and Treatment Effect of NAC-Observations In Vitro and In Vivo.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- The pivotal role of mitochondria in the pathogenesis and treatment of liver failure: a comprehensive review.Molecular and cellular biochemistry · 2026Review
- Functional analysis of novel and recurrent RINT1 variants in patients with infantile liver dysfunction.Journal of human genetics · 2026Article
- Bidirectional Causal Associations Between Plasma Metabolites and Parkinson's Disease.Molecular neurobiology · 2025Article
- Recurrent acute liver failure and neutropenia caused by a novel homozygous RINT1 variant: a brief report of phenotypic expansion and population-specific findings.Human genomics · 2025Article
- Cytokine-Induced Cytotoxicity and Extracellular Matrix Abnormalities in Hepatocytes Derived From RAD50-Interacting Protein 1-Deficient Induced Pluripotent Stem Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Germline variants detected by multigene panel testing in patients with suspected hereditary breast cancer.Surgery today · 2025Article
- An update on autophagy disorders.Journal of inherited metabolic disease · 2025Review
- Disorders of vesicular trafficking presenting with recurrent acute liver failure: NBAS, RINT1, and SCYL1 deficiency.Journal of inherited metabolic disease · 2025Review
- Mitochondria and Lipid Droplets: Focus on the Molecular Structure of Contact Sites in the Pathogenesis of Metabolic Syndrome.Current medicinal chemistry · 2025Review
- Recurrent fever-associated acute liver failure and cranial dysmorphism in children caused by RINT1 gene mutations: a rare case report.Frontiers in pediatrics · 2025Article
- Tilorone mitigates the propagation of α-synucleinopathy in a midbrain-like organoid model.Journal of translational medicine · 2024Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic RINT1 loss-of-function variants who presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype. Our functional and lipidomic analyses provided evidence that pathogenic RINT1 variants induce defective lipid-droplet biogenesis and profound lipid abnormalities in fibroblasts and plasma that impact both neutral lipid and phospholipid metabolism, including decreased triglycerides and diglycerides, phosphatidylcholine/phosphatidylserine ratios, and inhibited Lands cycle. Further, RINT1 mutations induced intracellular ROS production and reduced ATP synthesis, affecting mitochondria with membrane depolarization, aberrant cristae ultrastructure, and increased fission. Altogether, our results highlighted the pivotal role of RINT1 in lipid metabolism and mitochondria function, with a profound effect in central nervous system development.
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