Supercomplex-Associated Cox26 Protein Binds to Cytochrome \u3cem\u3ec\u3c/em\u3e Oxidase

Here we identified a hydrophobic 6.4 kDa protein, Cox26, as a novel component of yeast mitochondrial supercomplex comprising respiratory complexes III and IV. Multi-dimensional native and denaturing electrophoretic techniques were used to identify proteins interacting with Cox26. The majority of the Cox26 protein was found non-covalently bound to the complex IV moiety of the III–IV supercomplexes. A population of Cox26 was observed to exist in a disulfide bond partnership with the Cox2 subunit of complex IV. No pronounced growth phenotype for Cox26 deficiency was observed, indicating that Cox26 may not play a critical role in the COX enzymology, and we speculate that Cox26 may serve to regulate or support the Cox2 protein. Respiratory supercomplexes are assembled in the absence of the Cox26 protein, however their pattern slightly differs to the wild type III–IV supercomplex appearance. The catalytic activities of complexes III and IV were observed to be normal and respiration was comparable to wild type as long as cells were cultivated under normal growth conditions. Stress conditions, such as elevated temperatures resulted in mild decrease of respiration in non-fermentative media when the Cox26 protein was absent

Neonatal Hemochromatosis: Systematic Review of Prenatal Ultrasound Findings—Is There a Place for MRI in the Diagnostic Process?

Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis

Functional organization of the yeast proteome by systematic analysis of protein complexes.

Most cellular processes are carried out by multiprotein complexes. The identification and analysis of their components provides insight into how the ensemble of expressed proteins (proteome) is organized into functional units. We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. We processed 1,739 genes, including 1,143 human orthologues of relevance to human biology, and purified 589 protein assemblies. Bioinformatic analysis of these assemblies defined 232 distinct multiprotein complexes and proposed new cellular roles for 344 proteins, including 231 proteins with no previous functional annotation. Comparison of yeast and human complexes showed that conservation across species extends from single proteins to their molecular environment. Our analysis provides an outline of the eukaryotic proteome as a network of protein complexes at a level of organization beyond binary interactions. This higher-order map contains fundamental biological information and offers the context for a more reasoned and informed approach to drug discovery

Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies.

Although mutations in CYTB (cytochrome b) or BCS1L have been reported in isolated defects of mitochondrial respiratory chain complex III (cIII), most cIII-defective individuals remain genetically undefined. We identified a homozygous nonsense mutation in the gene encoding tetratricopeptide 19 (TTC19) in individuals from two families affected by progressive encephalopathy associated with profound cIII deficiency and accumulation of cIII-specific assembly intermediates. We later found a second homozygous nonsense mutation in a fourth affected individual. We demonstrated that TTC19 is embedded in the inner mitochondrial membrane as part of two high-molecular-weight complexes, one of which coincides with cIII. We then showed a physical interaction between TTC19 and cIII by coimmunoprecipitation. We also investigated a Drosophila melanogaster knockout model for TTC19 that showed low fertility, adult-onset locomotor impairment and bang sensitivity, associated with cIII deficiency. TTC19 is a putative cIII assembly factor whose disruption is associated with severe neurological abnormalities in humans and flies