Fine-tuning of the respiratory complexes stability and supercomplexes assembly in cells defective of complex III

In this study, we used genetically and biochemically well characterized cells bearing the pathogenic microdeletion m.15,649–15,666 (ΔI300-P305) in MT-CYB gene, to investigate the effects of an assembly-hampered CIII on the re-organization of supercomplexes. First, we found that this mutation also affects the stability of both CI and CIV, and evidences the occurrence of a preferential structural interaction between CI and CIII2, yielding a small amount of active CI + CIII2 supercomplex. Indeed, a residual CI + CIII combined redox activity, and a low but detectable ATP synthesis driven by CI substrates are detectable, suggesting that the assembly of CIII into the CI + CIII2 supercomplex mitigates the detrimental effects of MT-CYB deletion. Second, measurements of oxygen consumption and ATP synthesis driven by NADH-linked and FADH2-linked substrates alone, or in combination, indicate a common ubiquinone pool for the two respiratory pathways. Finally, we report that prolonged incubation with rotenone enhances the amount of CI and CIII2, but reduces CIV assembly. Conversely, the antioxidant N-acetylcysteine increases CIII2 and CIV2 and partially restores respirasome formation. Accordingly, after NAC treatment, the rate of ATP synthesis increases by two-fold compared with untreated cell, while the succinate level, which is enhanced by the homoplasmic mutation, markedly decreases. Overall, our findings show that fine-tuning the supercomplexes stability improv...
Source: Biochimica et Biophysica Acta (BBA) Bioenergetics - Category: Biochemistry Source Type: research

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ConclusionKagami –Ogata syndrome should have been suspected because of the presence of polyhydramnios and omphalocele during pregnancy. Respiratory insufficiency soon after birth, because of a small thorax, is expected in this disease and a diagnosis during pregnancy may have enabled appropriate care after birth.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
In conclusion, we reconfirm the utility of performing a genome-wide scan to achieve a differential diagnosis in patients with SRS or similar features and to highlight novel chromosome alterations associated with SRS and growth retardation disorders.
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Abstract OBJECTIVE: The purpose of this study was to analyze the relationship between cranial base, cerebellar, craniofacial, and velopharyngeal (VP) variables in individuals with 22q11.2 deletion syndrome (22q11DS). METHODS: Thirteen typically developing healthy children and 13 age- and sex-matched individuals with 22q11DS completed a magnetic resonance imaging scan, which was used to examine craniofacial and VP variables. RESULTS: A statistically significant difference was noted in cerebellum volumes, F 1,24 = 7.947, P = .010, posterior nasal spine to posterior pharyngeal wall (PNS-PPW), F 1,24 = 4.878...
Source: The Cleft Palate-Craniofacial Journal - Category: ENT & OMF Authors: Tags: Cleft Palate Craniofac J Source Type: research
Conclusion: The CNVs in 7q11.23 results in many clinical manifestations, but the specificity of clinical features is not high. This study demonstrated that BoBs combined with CMA allows prenatal diagnosis of CNVs involving 7q11.23, and provide a clinical basis for prenatal diagnosis and genetic counseling of such CNVs. PMID: 31402733 [PubMed - as supplied by publisher]
Source: Fetal and Pediatric Pathology - Category: Pathology Tags: Fetal Pediatr Pathol Source Type: research
ConclusionsThe lack of harmonization of practices concerning the prenatal diagnosis of IRAA may have consequences for patients care. Therefore, we begin a national multicentric retrospective study between 2010 to 2019 to collect data about the management of prenatal diagnosis of IRAA: ARCADE (2019_IRB-MTP_03-31) that aims to evaluate the reliability of antenatal diagnosis of IRAA in terms of anatomy and functional prognosis to harmonize the medical care for this population.
Source: Archives of Cardiovascular Diseases Supplements - Category: Cardiology Source Type: research
Abstract OBJECTIVE: The 22q11.2 deletion syndrome (22q11.2DS) is the most common genetic cause of velopharyngeal dysfunction; however, limited information exists regarding variations in velopharyngeal anatomy in this clinically challenging population. The purpose of this study was to examine velopharyngeal characteristics among young children with 22q11.2DS in comparison to a normative cohort using an innovative, nonsedated magnetic resonance imaging (MRI) scanning protocol. METHODS: Fifteen children with 22q11.2DS and 15 age- and gender-matched controls with normal velopharyngeal anatomy (ages 4-12) successf...
Source: The Cleft Palate-Craniofacial Journal - Category: ENT & OMF Authors: Tags: Cleft Palate Craniofac J Source Type: research
Conclusion: There may be an association between schizophrenia and HNPP. In observational studies, the deletion of interest (chromosome 17p12) was nearly 10 times more common in schizophreniform patients than in controls. This potential association could be pathophysiologically explained by the role of PMP22, which is mainly expressed in the peripheral nervous system. However, PMP22 mRNA and protein can also be found in the brain. PMP22 seems to play an important role in regulating cell growth and myelination, functions that are disturbed in schizophrenia. Such a connection obviously cannot be clarified on the basis of one ...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Discussion In this section, we discuss the mechanisms responsible for lymphomagenesis in the various inborn errors of immunity and provide an overview of the treatment. Defects in Immune Responses That Predispose to Lymphomagenesis in PIDDs The complex immune mechanisms and their interplay that predisposes to neoplastic transformation of B or T cells and development of lymphomas in PIDD patients has not been fully elucidated. However, it is expected that the etiology in most cases is multifactorial and related to a dynamic regulation of immune response and environmental triggers (Figure 3). An underlying intrinsic susce...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This study assessed whether neurocognition, functional capacity and metacognitive ability in FEP predicted functional outcome three years later. Methods: Eighty individuals with First Episode Psychosis were re-contacted after an average 3 years (range: 26–45 month follow-up) from baseline. Twenty-six participants (33%) completed completed measures of neurocognition, metacognition, functional capacity, functional outcome (hours spent in structured activity per week) and psychopathology at baseline and at follow-up. Results: Individual regression analyses demonstrated neurocognition, functional capacity, and metacogn...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Conclusion: This case represents an example of diagnostic and therapeutic challenges of catatonic schizophrenia in high-functioning autism due to clinical and neurobiological overlaps of these conditions. We discuss clinical features together with pathophysiological concepts of both conditions. Furthermore, we tackle social and legal hurdles in Germany that naturally arise in these patients. Finally, we present diagnostic “red flags” that can be used to rationally select and conduct current recommended diagnostic assessments if there is a suspicion of ASD in patients with catatonic syndrome in order to provide ...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
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