ArticleAnnals of neurology2018
Pathological mechanisms underlying single large-scale mitochondrial DNA deletions.
Article in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
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- Distinct Mitochondrial DNA Deletion Profiles in Pediatric B- and T-ALL During Diagnosis, Remission, and Relapse.International journal of molecular sciences · 2025Article
- Bayesian classification of OXPHOS deficient skeletal myofibres.PLoS computational biology · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Mapping mitochondrial morphology and function: COX-SBFSEM reveals patterns in mitochondrial disease.Communications biology · 2025Article
- Fatal pneumonia in a patient with Kearns-Sayre syndrome case report and literature review.Frontiers in medicine · 2025Article
- Genetic landscape of primary mitochondrial diseases in children and adults using molecular genetics and genomic investigations of mitochondrial and nuclear genome.Orphanet journal of rare diseases · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Mitochondrial complex I deficiency stratifies idiopathic Parkinson's disease.Nature communications · 2024Article
- Heterogeneous Antibiotic Resistance Gene Removal Impedes Evaluation of Constructed Wetlands for Effective Greywater Treatment.Antibiotics (Basel, Switzerland) · 2024Article
- Mitochondrially Targeted Gene Therapy Rescues Visual Loss in a Mouse Model of Leber's Hereditary Optic Neuropathy.International journal of molecular sciences · 2023Article
- Interactions of mitochondrial and skeletal muscle biology in mitochondrial myopathy.The Biochemical journal · 2023Review
- Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1/PRKN-linked Parkinson's disease.Brain : a journal of neurology · 2023Article
- Genetic testing for mitochondrial disease: the United Kingdom best practice guidelines.European journal of human genetics : EJHG · 2023Article
- Resistance Exercise Training Rescues Mitochondrial Dysfunction in Skeletal Muscle of Patients with Myotonic Dystrophy Type 1.Journal of neuromuscular diseases · 2023Article
- Single Cell Analysis of Mitochondrial DNA Deletions.Methods in molecular biology (Clifton, N.J.) · 2023Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveSingle, large-scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large-scale mtDNA deletions in skeletal muscle.
methodsWe investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large-scale mtDNA deletions. Mitochondrial respiratory chain deficiency in skeletal muscle biopsies was quantified by immunoreactivity levels for complex I and complex IV proteins. Single muscle fibers with varying degrees of deficiency were selected from 6 patient biopsies for determination of mtDNA deletion level and copy number by quantitative polymerase chain reaction.
resultsWe have defined 3 "classes" of single, large-scale deletion with distinct patterns of mitochondrial deficiency, determined by the size and location of the deletion. Single fiber analyses showed that fibers with greater respiratory chain deficiency harbored higher levels of mtDNA deletion with an increase in total mtDNA copy number. For the first time, we have demonstrated that threshold levels for complex I and complex IV deficiency differ based on deletion class.
interpretationCombining genetic and immunofluorescent assays, we conclude that thresholds for complex I and complex IV deficiency are modulated by the deletion of complex-specific protein-encoding genes. Furthermore, removal of mt-tRNA genes impacts specific complexes only at high deletion levels, when complex-specific protein-encoding genes remain. These novel findings provide valuable insight into the pathogenic mechanisms associated with these mutations. Ann Neurol 2018;83:115-130.
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