Refine
Year of publication
Language
- English (62) (remove)
Has Fulltext
- yes (62)
Is part of the Bibliography
- no (62)
Keywords
- Proteomics (3)
- complexome profiling (3)
- mitochondria (3)
- Aging (2)
- Calpain (2)
- Complex I (2)
- NADPH oxidase (2)
- Podospora anserina (2)
- Reactive oxygen species (2)
- aging (2)
- bioenergetics (2)
- long non-coding RNA (2)
- mitochondrial disease (2)
- A/D transition (1)
- AAA+ disaggregase (1)
- Activities of daily living (1)
- Adult neurogenesis (1)
- Alternative oxidase (1)
- Apoptosis (1)
- Ataxia (1)
- Autoimmune vasculopathy (1)
- Autophagy (1)
- BIAM switch assay (1)
- BIAM-switch (1)
- BPTF (1)
- Behavior (1)
- Biochemistry (1)
- Brain (1)
- Calcium calmodulin kinase (1)
- Cardiac infarction (1)
- Cardiology (1)
- Cardiomyopathy (1)
- Cell signalling (1)
- Chaperone (1)
- Chemical modification (1)
- Chemiluminescence (1)
- ClpB (1)
- Complex II (1)
- Complexome profiling (1)
- Conformational change (1)
- Cortex (1)
- DNA Damage (1)
- DNA methylation (1)
- Data visualization (1)
- Database (1)
- ERAL1 (1)
- Endothelial cell (EC) (1)
- Endothelial cells (1)
- Endothelial protein C receptor (1)
- FAIR (1)
- Flavin mononucleotide (1)
- G3BP1 (1)
- HARS2 (1)
- HSP (hereditary spastic paraplegia) (1)
- Heart (1)
- Heart transplantation (1)
- Hig1 (1)
- Hypoxia inducible factor (1)
- ICAM-1 (1)
- IL-1β (1)
- Innate immunity (1)
- IntelliCage (1)
- Isoforms (1)
- KLHL11 (1)
- LARS2 (1)
- Lactic acidosis (1)
- Leukodystrophy (1)
- LncRNA - long noncoding RNA (1)
- Long non-coding RNAs (1)
- Lucigenin (1)
- Lysosome (1)
- MEIS homeodomain protein (1)
- MTRNR1 (1)
- Mass spectrometry (1)
- Membrane assays (1)
- Microparticles (1)
- Mitochondria (1)
- Mitochondrial ROS (1)
- Mitochondrial amino acid tRNA synthetases (1)
- Mitochondrial complex I (1)
- Mitochondrial disease (1)
- Mitochondrial disorder (1)
- Mitochondrial dysfunction (1)
- N-hydroxysuccinimide (1)
- N471D strumpellin knock-in mice (1)
- NADH:ubiquinone oxidoreductase (1)
- NDUFA6 (1)
- NDUFAF8 (1)
- NURF (1)
- Neonatal (1)
- Neurodegeneration (1)
- Nitric oxide (1)
- Nox (1)
- Nox4 (1)
- OXPHOS (1)
- POLG (1)
- PRLTS3 (1)
- Parkinson’s disease (1)
- Perrault syndrome (1)
- Play (1)
- Pleasure (1)
- Post-translational modifications (1)
- Posttranslational modification (1)
- Prognosis (1)
- Progranulin (1)
- Protein complex (1)
- Protein tyrosine modification (1)
- RNA Biology (1)
- RNA turnover (1)
- RNA, long noncoding (1)
- Rapamycin (1)
- Rcf1 (1)
- Redox modification (1)
- Redoxin (1)
- Release of mtDNA and mtRNA (1)
- Respiratory chain (1)
- Reverse electron transfer (1)
- SDH (1)
- SPG8 (1)
- Senescence (1)
- Starvation (1)
- Stem cell (1)
- Stroke (1)
- Stroke genetics (1)
- Subventricular zone (1)
- Superoxide (1)
- TRIM25 (1)
- TWINKLE (1)
- TWNK (1)
- Tissue-specificity (1)
- Transcription factor (1)
- Treatment (1)
- Ubiquitin (1)
- Ubiquitin ligase (1)
- Vitamin (1)
- WASH complex subunit 5 (1)
- adaptive cardiac remodelling (1)
- alternative oxidase (1)
- alternative splicing (1)
- angiogenesis (1)
- aortic aneurysm (1)
- assembly (1)
- ataxia (1)
- atherosclerosis (1)
- cGAS-STING (1)
- cancer metastases (1)
- cardiac ischaemia‐reperfusion (1)
- cardiolipin (1)
- cardiovascular disease (1)
- caspase-2 (1)
- chemotherapy resistance (1)
- colon carcinoma cells (1)
- complex I (1)
- complex I deficiency (1)
- crista junction (1)
- cristae (1)
- cytochrome c oxidase (complex IV) (1)
- data repositories (1)
- diabetes mellitus (1)
- electron transport chain (1)
- epigenomics (1)
- gene expression (1)
- glioblastoma (1)
- hypertension, pulmonary (1)
- i-AAA protease (1)
- intrinsic apoptosis (1)
- ischemia (1)
- leukodystrophy (1)
- long non-coding RNAs (1)
- macrophage (1)
- mass spectrometry (1)
- matrix metalloproteinase (1)
- membrane protein complex (1)
- membrane structure (1)
- metabolomics (1)
- molecular diagnosis (1)
- mouse (1)
- neovascularization, physiologic (1)
- nonsense-mediated mRNA decay (1)
- polyunsaturated fatty acid (1)
- proliferation (1)
- protein complexes (1)
- protein quality control (1)
- protein–protein interaction (1)
- proteomics (1)
- reactive oxygen species (1)
- remodeling (1)
- smooth muscle cell (1)
- strumpellin (1)
- temperature (1)
- therapeutics (1)
- tight junctions (1)
- vascular disease (1)
- vascular integrity (1)
- vascular remodeling (1)
- yeast (1)
Institute
Biallelic mutations in TMEM126B cause severe complex i deficiency with a variable clinical phenotype
(2016)
Complex I deficiency is the most common biochemical phenotype observed in individuals with mitochondrial disease. With 44 structural subunits and over 10 assembly factors, it is unsurprising that complex I deficiency is associated with clinical and genetic heterogeneity. Massively parallel sequencing (MPS) technologies including custom, targeted gene panels or unbiased whole-exome sequencing (WES) are hugely powerful in identifying the underlying genetic defect in a clinical diagnostic setting, yet many individuals remain without a genetic diagnosis. These individuals might harbor mutations in poorly understood or uncharacterized genes, and their diagnosis relies upon characterization of these orphan genes. Complexome profiling recently identified TMEM126B as a component of the mitochondrial complex I assembly complex alongside proteins ACAD9, ECSIT, NDUFAF1, and TIMMDC1. Here, we describe the clinical, biochemical, and molecular findings in six cases of mitochondrial disease from four unrelated families affected by biallelic (c.635G>T [p.Gly212Val] and/or c.401delA [p.Asn134Ilefs∗2]) TMEM126B variants. We provide functional evidence to support the pathogenicity of these TMEM126B variants, including evidence of founder effects for both variants, and establish defects within this gene as a cause of complex I deficiency in association with either pure myopathy in adulthood or, in one individual, a severe multisystem presentation (chronic renal failure and cardiomyopathy) in infancy. Functional experimentation including viral rescue and complexome profiling of subject cell lines has confirmed TMEM126B as the tenth complex I assembly factor associated with human disease and validates the importance of both genome-wide sequencing and proteomic approaches in characterizing disease-associated genes whose physiological roles have been previously undetermined.