Novel MTND1 mutations cause isolated exercise intolerance, complex I deficiency and increased assembly factor expression

Complex I (CI) is the largest of the five multi-subunit complexes constituting the human oxidative phosphorylation (OXPHOS) system. Seven of its catalytic core subunits are encoded by mitochondrial DNA (ND1-ND6, ND4L), with mutations in all seven having been reported in association with isolated CI deficiency. We investigated two unrelated adult patients presenting with marked exercise intolerance, persistent lactic acidaemia and severe, muscle-restricted isolated CI deficiency associated with subsarcolemmal mitochondrial accumulation. Screening of the mitochondrial genome detected novel mutations in the MTND1 gene, encoding subunit of CI (Patient 1, m.3365T>C predicting p.(Leu20Pro); Patient 2, m.4175G>A predicting p.(Trp290*)) at high levels of mitochondrial DNA heteroplasmy in skeletal muscle. We evaluated the effect of these novel MTND1 mutations on complex assembly showing that CI assembly although markedly reduced, was viable, in the absence of detectable ND1 signal. Real-time PCR and western blotting showed overexpression of different CI assembly factor transcripts and proteins in patient tissue. Together our data indicate that the mechanism underlying the expression of the biochemical defect may involve a compensatory response to the novel MTND1 gene mutations, promoting assembly factor upregulation and stabilisation of respiratory chain supercomplexes, resulting in partial rescue of the clinical phenotype.
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research

Related Links:

CONCLUSION: In the outpatient clinic specializing in oral anticoagulation, patients add more specific beliefs about the interference of vitamin K-rich diet on coagulation, when compared to those in the general cardiology outpatient clinic. PMID: 31618372 [PubMed - in process]
Source: Revista gaucha de enfermagem EENFUFRGS - Category: Nursing Tags: Rev Gaucha Enferm Source Type: research
CONCLUSION: The Tracer Methodology is used for evaluating and improving the quality of care. PMID: 31618371 [PubMed - in process]
Source: Revista gaucha de enfermagem EENFUFRGS - Category: Nursing Tags: Rev Gaucha Enferm Source Type: research
Publication date: Available online 16 October 2019Source: Ticks and Tick-borne DiseasesAuthor(s): Nicole E. Breuner, Shelby L. Ford, Andrias Hojgaard, Lynn M. Osikowicz, Christina M. Parise, Maria F. Rosales Rizzo, Ying Bai, Michael L. Levin, Rebecca J. Eisen, Lars EisenAbstractThe invasive, human-biting Asian longhorned tick, Haemaphysalis longicornis, was detected in New Jersey in the eastern United States in August of 2017 and by November of 2018 this tick had been recorded from 45 counties across 9 states, primarily along the Eastern Seaboard. The establishment of H. longicornis in the United States has raised the ques...
Source: Ticks and Tick borne Diseases - Category: Zoology Source Type: research
Publication date: Available online 16 October 2019Source: Ticks and Tick-borne DiseasesAuthor(s): Jinming Wang, Jifei Yang, Shandian Gao, Aihong Liu, Muhammad Rashid, Youquan Li, Zhijie Liu, Junlong Liu, Guangyuan Liu, Jianxun Luo, Guiquan Guan, Hong YinAbstractBovine theileriosis, caused by protozoan parasites of the genus Theileria, presents with various clinical symptoms. In cattle, clinical presentations and outcomes of bovine theileriosis are closely correlated with the causative Theileria spp. Thus, accurate detection and discrimination of Theileria spp. are essential for epidemiological studies and for provision of ...
Source: Ticks and Tick borne Diseases - Category: Zoology Source Type: research
Publication date: Available online 16 October 2019Source: Small Ruminant ResearchAuthor(s): Alison M. Lee, Alan Wolfe, Joseph P. Cassidy, John Moriarty, Ronan O’Neill, Claire Fahy, Emily Connaghan, Chris Cousens, Mark P. Dagleish, Maire C. McElroy, Locksley L. McV. MessamAbstractJaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA). JSRV infection is usually detected post-mortem by macroscopic and histological examination of lungs for lesions of OPA. Subsequently, the presence of JSRV may be confirmed using polymerase chain reaction (PCR) on tumour tissue. Our goal was to d...
Source: Small Ruminant Research - Category: Zoology Source Type: research
This study not only represents the most systematic analysis of codon usage patterns in PEDV orf3 genes, but also provides a basic shaping mechanism of the codon usage bias.
Source: Research in Veterinary Science - Category: Veterinary Research Source Type: research
Publication date: Available online 16 October 2019Source: Research in Veterinary ScienceAuthor(s): Baolin Song, Qianmei Zeng, Yuan Liu, Bangyuan WuAbstractAbundant evidence now supports the idea that methionine deficiency has negative effects on chicken healthy especially in the aspect of cell cycle regulation and apoptosis. But, lacking of knowledge is the evaluation on metabolic organs. To test the effect of methionine deficiency on the kidney, we assessed the apoptosis and the cell cycle of kidney induced by methionine deficiency by the methods of TdT-mediated dUTP Nick-End Labeling (TUNEL), flow cytometry (FCM), quanti...
Source: Research in Veterinary Science - Category: Veterinary Research Source Type: research
Publication date: Available online 16 October 2019Source: Research in Veterinary ScienceAuthor(s): Pascal Rainard
Source: Research in Veterinary Science - Category: Veterinary Research Source Type: research
Publication date: Available online 16 October 2019Source: Research in Veterinary ScienceAuthor(s): L.C. Rhades, M. Larzábal, A. Bentancor, J. Sabio y García, F.J. Babinec, A. Cataldi, N. Amigo, V.N. Baldone, L. Urquiza, P.J. Delicia, M.C. FortAbstractBovines are the primary reservoir of enterohemorrhagic Escherichia coli (EHEC) O157:H7 and the main source of its transmission to humans. Here, we present a one-year longitudinal study of fecal shedding of E. coli O157. E. coli O157 obtained from recto-anal mucosal samples were characterized by multiplex PCR. The E. coli O157 prevalence ranged from 0.84% in July ...
Source: Research in Veterinary Science - Category: Veterinary Research Source Type: research
PMID: 31617895 [PubMed - in process]
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research
More News: Biomedical Science | Genetics | Respiratory Medicine | Science | Sports Medicine