Search

HIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction. The role of platelet mitochondrial dysfunction in thrombosis, immunoregulation and age-related diseases is increasingly appreciated. Here, we studied platelet mitochondrial DNA content (mtDNApl) and mitochondrial function in people living with HIV (PLHIV) and related this to platelet function. In a cohort of 208 treated PLHIV and 56 uninfected controls, mtDNApl was quantified, as well as platelet activation, platelet agonist-induced reactivity and inflammation by circulating factors and flow cytometry. In a subgroup of participants, the metabolic activity of platelets was further studied by mitochondrial function tests and the Seahorse Flux Analyzer. PLHIV had significantly lower mtDNApl compared to controls (8.5 copies/platelet (IQR: 7.0–10.7) vs. 12.2 copies/platelet (IQR: 9.5–16.6); p pl. PLHIV also had reduced ex vivo platelet reactivity and mean platelet volume compared to controls. MtDNApl correlated positively with both platelet parameters and correlated negatively with inflammatory marker sCD163. Mitochondrial function tests in a subgroup of participants confirmed the presence of platelet mitochondrial respiration defects. Platelet mitochondrial function is disturbed in PLHIV, which may contribute to platelet dysfunction and subsequent complications. Interventions targeting the preservation of normal platelet mitochondrial function may ultimately prove beneficial for PLHIV.

Mitochondrial complex I deficiency is the most frequent mitochondrial disorder presenting in childhood and the mutational spectrum is highly heterogeneous. The NDUFB11 gene is one of the recently identified genes, which is located in the short arm of the X-chromosome. Here we report clinical, biochemical, functional and genetic findings of two male patients with lactic acidosis, hypertrophic cardiomyopathy and isolated complex I deficiency due to de novo hemizygous mutations (c.286C > T and c.328C > T) in the NDUFB11 gene. Neither of them had any skin manifestations. The NDUFB11 gene encodes a relatively small integral membrane protein NDUFB11, which is essential for the assembly of an active complex I. The expression levels of this protein was decreased in both patient cells and a lentiviral complementation experiment also supported the notion that the complex I deficiency in those two patients is caused by NDUFB11 genetic defects. Our findings together with a review of the thirteen previously described patients demonstrate a wide spectrum of clinical features associated with NDUFB11-related complex I deficiency. However, histiocytoid cardiomyopathy and/or congenital sideroblastic anemia could be indicative for mutation in the NDUFB11 gene, while the clinical manifestation of the same mutation can be highly variable.

Mitochondrial respiratory chain complex I consists of 44 different subunits and can be subgrouped into three functional modules: the Q-, the P- and the N-module. NDUFAF4 (C6ORF66) is an assembly factor of complex I that associates with assembly intermediates of the Q-module. Via exome sequencing, we identified a homozygous missense variant in a complex I-deficient patient with Leigh syndrome. Supercomplex analysis in patient fibroblasts revealed specifically altered stoichiometry. Detailed assembly analysis of complex I, indicative of all of its assembly routes, showed an accumulation of parts of the P- and the N-module but not the Q-module. Lentiviral complementation of patient fibroblasts with wild-type NDUFAF4 rescued complex I deficiency and the assembly defect, confirming the causal role of the variant. Our report on the second family affected by an NDUFAF4 variant further characterizes the phenotypic spectrum and sheds light into the role of NDUFAF4 in mitochondrial complex I biogenesis.

The phylogenetic position of diatoms belonging to the genus Attheya is presently under debate. Species belonging to this genus have been placed in the subclasses Chaetocerotophycidae and Biddulphiophycidae, but published phylogenetic trees based on 18S rDNA, morphology, and sexual reproduction indicate that this group of diatoms may be a sister group of the pennates. To clarify the position of Attheya, we studied the morphology, 18S rDNA, 16S rDNA of the chloroplasts, the rbcL large subunit (LSU) sequences of the chloroplasts, and the sterol composition of three different strains of Attheya septentrionalis (Østrup) R. M. Crawford and one strain of Attheya longicornis R. M. Crawford et C. Gardner. These data were compared with data from more than 100 other diatom species, covering the whole phylogenetic tree, with special emphasis on species belonging to the genera that have been suggested to be related to the genus Attheya. All data suggest that the investigated Attheya species form a separate group of diatoms, and there is no indication that they belong to either the Chaetocerotophycidae or the Biddulphiophycidae. Despite applying these various approaches, we were unable to determine the exact phylogenetic position of the investigated Attheya species within the diatoms.

The phylogenetic position of diatoms belonging to the genus Attheya is presently under debate. Species belonging to this genus have been placed in the subclasses Chaetocerotophycidae and Biddulphiophycidae, but published phylogenetic trees based on 18S rDNA, morphology, and sexual reproduction indicate that this group of diatoms may be a sister group of the pennates. To clarify the position of Attheya, we studied the morphology, 18S rDNA, 16S rDNA of the chloroplasts, the rbcL large subunit (LSU) sequences of the chloroplasts, and the sterol composition of three different strains of Attheya septentrionalis (Ostrup) R. M. Crawford and one strain of Attheya longicornis R. M. Crawford et C. Gardner. These data were compared with data from more than 100 other diatom species, covering the whole phylogenetic tree, with special emphasis on species belonging to the genera that have been suggested to be related to the genus Attheya. All data suggest that the investigated Attheya species form a separate group of diatoms, and there is no indication that they belong to either the Chaetocerotophycidae or the Biddulphiophycidae. Despite applying these various approaches, we were unable to determine the exact phylogenetic position of the investigated Attheya species within the diatoms.

Contains fulltext : 97138.pdf (Publisher’s version ) (Closed access) The oxidative phosphorylation (OXPHOS) system is under control of both the mitochondrial and the nuclear genomes; 13 subunits are synthesized by the mitochondrial translation machinery. We report a patient with Cornelia de Lange-like dysmorphic features, brain abnormalities and hypertrophic cardiomyopathy, and studied the genetic defect responsible for the combined OXPHOS complex I, III and IV deficiency observed in fibroblasts. The combination of deficiencies suggested a primary defect associated with the synthesis of mitochondrially encoded OXPHOS subunits. Analysis of mitochondrial protein synthesis revealed a marked impairment in mitochondrial translation. Homozygosity mapping and sequence analysis of candidate genes revealed a homozygous mutation in MRPS22, a gene encoding a mitochondrial ribosomal small subunit protein. The mutation predicts a Leu215Pro substitution at an evolutionary conserved site. Mutations in genes implicated in Cornelia de Lange syndrome or copy number variations were not found. Transfection of patient fibroblasts, in which MRPS22 was undetectable, with the wild-type MRPS22 cDNA restored the amount and activity of OXPHOS complex IV, as well as the 12S rRNA transcript level to normal values. These findings demonstrate the pathogenicity of the MRPS22 mutation and stress the significance of mutations in nuclear genes, including genes that have no counterparts in lower species like bacteria and yeast, for mitochondrial translation defects.

Crenarchaeota, single-celled planktonic Archaea, account for up to a third of all prokaryotic cells in the oceans on some estimates, and are thought to be responsible for the majority of ammonia oxidation in terrestrial and marine environments. However, recent studies have suggested that not all species are autotrophic. Using a comprehensive data set it is now shown that a significant proportion of marine crenarchaeota lack the genes required for ammonia oxidation, suggesting that they are heterotrophs, consuming organic matter as their main carbon and energy source. These results provide insight into the physiology of this important group of microorganism and its impact on global nutrient cycles. Crenarchaeota, which comprise the most abundant clade of organisms on Earth, are believed to be responsible for the majority of ammonia oxidation in terrestrial and marine environments. But recent studies have suggested that not all species are autotrophic. Using a comprehensive dataset, it is now shown that a significant proportion of marine crenarchaeota lack the genes required for ammonia oxidation, suggesting that they are heterotrophs. Aerobic nitrification of ammonia to nitrite and nitrate is a key process in the oceanic nitrogen cycling mediated by prokaryotes1. Apart from Bacteria belonging to the β- and γ-Proteobacteria involved in the first nitrification step, Crenarchaeota have recently been recognized as main drivers of the oxidation of ammonia to nitrite in soil as well as in the ocean, as indicated by the dominance of archaeal ammonia monooxygenase (amoA) genes over bacterial amoA2,3. Evidence is accumulating that archaeal amoA genes are common in a wide range of marine systems3,4,5,6. Essentially, all these reports focused on surface and mesopelagic (200–1,000 m depth) waters, where ammonia concentrations are higher than in waters below 1,000 m depth. However, Crenarchaeota are also abundant in the water column below 1,000 m, where ammonia concentrations are extremely low. Here we show that, throughout the North Atlantic Ocean, the abundance of archaeal amoA genes decreases markedly from subsurface waters to 4,000 m depth, and from subpolar to equatorial deep waters, leading to pronounced vertical and latitudinal gradients in the ratio of archaeal amoA to crenarchaeal 16S ribosomal RNA (rRNA) genes. The lack of significant copy numbers of amoA genes and the very low fixation rates of dark carbon dioxide in the bathypelagic North Atlantic suggest that most bathypelagic Crenarchaeota are not autotrophic ammonia oxidizers: most likely, they utilize organic matter and hence live heterotrophically.