Generation of hiPSC lines from four pyridoxine-dependent epilepsy (PDE) patients carrying the variant c.1279G>C in ALDH7A1 in homozygosis.

ALDH7A1 encodes for the enzyme catalyzing the third step of the lysine degradation pathway. Biallelic pathogenic variants in ALDH7A1 are associated with pyridoxine dependent epilepsy (PDE), of which the c.1279G>C (p.Glu427Gln) variant is the most commonly reported variant and is carried by 30% of PDE patients with European ancestry. In this study, hiPSC lines derived from four PDE patients carrying the c.1279G>C variant in homozygosis in ALDH7A1 were generated and fully characterized. These hiPSC lines can contribute to better understand the molecular mechanism of disease underlying PDE as well as serving as a model system to evaluate new therapeutic strategies.

Generation of hiPSC lines from four glutaric aciduria type I (GA1) patients carrying pathogenic biallelic variants in GCDH.

GCDH encodes for the enzyme catalyzing the sixth step of the lysine degradation pathway. Autosomal recessive variants in GCDH are associated with glutaric aciduria type I (GA1), of which a wide genotypic spectrum of pathogenic variants have been described. In this study, hiPSC lines derived from four GA1 patients with different genotypes were generated and fully characterized. Two patients carry compound heterozygous variants in GCDH, while the other two patients carry a variant in homozygosis. These hiPSC lines can significantly contribute to better understand the molecular mechanism underlying GA1 and provide excellent models for the development of new therapeutic strategies.

Flexible processing of distractor stimuli under stress.

Acute stress is assumed to affect executive processing of stimulus information, although extant studies have yielded heterogeneous findings. The temporal flanker task, in which a target stimulus is preceded by a distractor of varying utility, offers a means of investigating various components involved in the adjustment of information processing and conflict control. Both behavioral and EEG data obtained with this task suggest stronger distractor-related response activation in conditions associated with higher predictivity of the distractor for the upcoming target. In two experiments we investigated distractor-related processing and conflict control after inducing acute stress (Trier Social Stress Test). Although the stressed groups did not differ significantly from unstressed control groups concerning behavioral markers of attentional adjustment (i.e., Proportion Congruent Effect), or event-related sensory components in the EEG (i.e., posterior P1 and N1), the lateralized readiness potential demonstrated reduced activation evoked by (predictive) distractor information under stress. Our results suggest flexible adjustment of attention under stress but hint at decreased usage of nominally irrelevant stimulus information for biasing response selection.

Preparation and persistence of deploying attention to locations or stimulus structures: Evidence from intermixed probe trials.

Attention can be directed to the global or local level of a visual stimulus (i.e., Navon figure). Previous studies yielded reliable trial-to-trial level switch costs (i.e., worse performance when responding to the other level than on a previous trial), even though level cueing effects indicated anticipatory deployment of attention to the upcoming target level. To investigate the interplay of attentional preparation and persistence, we applied a probe trial method assumed to ensure a high degree of preparation for the upcoming target level and minimizing stimulus-specific proactive interference. Mirroring previous findings obtained in the domain of spatial attention, we found evidence for anticipatory attentional focusing on global/local target levels but not for persistence of the attentional set adopted on the previous trial. In a second experiment, we prevented preparation for upcoming attentional demands (in both global-local and spatial attention tasks). This resulted in the modulation of performance (in critical probe trials) by the attentional demands of the predecessor trial. Together, our findings demonstrate sensitivity of the probe trial method for attentional persistence and raise the possibility that such persistence can be completely eliminated by sufficiently strong preparation for the attentional demands of the following trial.

Generation of an induced pluripotent stem cell line carrying biallelic deletions (SCTCi019-B) in ALDH7A1 using CRISPR/Cas9.

Biallelic pathogenic variants in ALDH7A1 are associated with pyridoxine-dependent epilepsy (PDE). ALDH7A1 encodes for the third enzyme of the lysine catabolism pathway. In this study a human isogenic ALDH7A1 knock-out iPSC line was created using CRISPR/Cas9 technology. One clone (SCTCi019-B) with biallelic deletions in ALDH7A1 was obtained and fully characterized, showing expression of pluripotency markers, a normal karyotype and no off-targets. Human-based models derived from this iPSC line will contribute to gain insights in the molecular mechanism of disease underlying PDE.

Limited impact of a bioeroding sponge, Cliona sp., on Ostrea chilensis from Foveaux Strait, New Zealand.

Bioeroding sponges can cause extensive damage to aquaculture and wild shellfish fisheries. It has been suggested that heavy sponge infestations that reach the inner cavity of oysters may trigger shell repair and lead to adductor detachment. Consequently, energy provision into shell repair could reduce the energy available for other physiological processes and reduce the meat quality of commercially fished oysters. Nevertheless, the impacts of boring sponges on oysters and other shellfish hosts are inconclusive. We studied the interaction between boring sponges and their hosts and examined potential detrimental effects on an economically important oyster species Ostrea chilensis from Foveaux Strait (FS), New Zealand. We investigated the effect of different infestation levels with the bioeroding sponge Cliona sp. on commercial meat quality, condition, reproduction, and disease susceptibility. Meat quality was assessed with an index based on visual assessments used in the FS O. chilensis fishery. Meat condition was assessed with a common oyster condition index, while histological methods were used to assess sex, gonad stage, reproductive capacity, and pathogen presence. Commercial meat quality and condition of O. chilensis were unaffected by sponge infestation. There was no relationship between sex ratio, gonad developmental stage, or gonad index and sponge infestation. Lastly, we found no evidence that sponge infestation affects disease susceptibility in O. chilensis. Our results suggest that O. chilensis in FS is largely unaffected by infestation with Cliona sp. and therefore reinforces the growing body of evidence that the effects of sponge infestation can be highly variable among different host species, environments, and habitats.

Exploring genotype-phenotype correlations in glutaric aciduria type 1.

Glutaric aciduria type 1 (GA1) is a rare neurometabolic disease caused by pathogenic variants in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). We performed an extensive literature search to collect data on GA1 patients, together with unpublished cases, to provide an up-to-date genetic landscape of GCDH pathogenic variants and to investigate potential genotype-phenotype correlation, as this is still poorly understood. From this search, 421 different GCDH pathogenic variants have been identified, including four novel variants; c.179T>C (p.Leu60Pro), c.214C>T (p.Arg72Cys), c.309G>C (p.Leu103Phe), and c.665T>C (p.Phe222Ser).The variants are mostly distributed across the entire gene; although variant frequency in GA1 patients is relatively high in the regions encoding for active domains of GCDH. To investigate potential genotype-phenotype correlations, phenotypic descriptions of 532 patients have been combined and evaluated using novel combinatorial analyses. To do so, various clinical phenotypes were determined for each pathogenic variant by combining the information of all GA1 patients reported with this pathogenic variant, and subsequently mapped onto the 2D and 3D GCDH protein structure. In addition, the predicted pathogenicity of missense variants was analyzed using different in silico prediction score models. Both analyses showed an almost similar distribution of the highly pathogenic variants across the GCDH protein, although some hotspots, including the active domain, were observed. Moreover, it was demonstrated that highly pathogenic variants are significantly correlated with lower residual enzyme activity and the most accurate estimation was achieved by the REVEL score. A clear correlation of the genotype and the clinical phenotype however is still lacking.

Generation of an induced pluripotent stem cell line carrying a biallelic deletion (SCTCi019-A) in GCDH using CRISPR/Cas9.

GCDH encodes for the enzyme catalyzing the sixth step of the lysine catabolism pathway. Biallelic pathogenic variants in GCDH have been associated with glutaric aciduria type 1 (GA1). In this study CRISPR/Cas9 technology was used to create an isogenic GCDH knock-out human iPSC line. One clone with a biallelic deletion (SCTCi019-A) in GCDH was obtained and fully characterized, revealing a normal karyotype, no off-targets detected and expression of pluripotency markers. This iPSC line can contribute to gain insights in the molecular mechanism of disease.

The effect of an informative 360-degree virtual reality video on anxiety for women visiting the one-stop clinic for abnormal uterine bleeding: A randomized controlled trial (VISION-trial).

OBJECTIVE: To evaluate the effect of an informative 360-degree virtual reality (VR) video on preoperative anxiety before visiting a one-stop clinic for abnormal uterine bleeding. STUDY DESIGN: A randomized controlled trial was performed in a teaching hospital in the Netherlands. A total of 83 women scheduled for a first consultation at the one-stop clinic between April 2017 and September 2017 were included in the analysis. All women received a standard information leaflet about the clinic. 40 women were randomized to receive a 360-degree VR-video of the clinic in addition. The primary outcome was change in the Visual Analogue Scale for Anxiety (VAS-A), measured at baseline (before randomization) and in the waiting room (before visit, after randomization). Anxiety assessed with the State-Trait Anxiety Inventory (STAI-S) was a secondary outcome. Other secondary outcomes included anxiety during the visit and the opinion of the women about the provided information. RESULTS: Only 27 out of the 40 women actually watched the VR-video. Women in the VR-group who actually watched the video reported lower levels of anxiety at baseline compared to women in the VR-group who did not watch the video. In the intention-to-treat analysis, there was no difference in change in anxiety between the VR-group and the control group (mean difference VAS-A = 0.07, 95% CI -0.96 to 1.10; mean difference STAI-S = 1.97, 95% CI -1.82 to 5.77). In the per-protocol analysis, women in the VR-group reported lower anxiety scores in the waiting room. However, the change in anxiety scores between baseline and waiting room was comparable in both groups. 31% of the women who watched the VR-video reported that the video resulted in a reduction of anxiety, 69% reported that the video is of added value and 65% would use a VR-video again in future. CONCLUSIONS: Adding the informative 360-degree VR-video to conventional information did not result in a reduction of anxiety prior to visiting the one-stop clinic. However, the majority of women who watched the video felt that it was of added value. Remarkable was that women who reported higher anxiety at baseline seemed less willing to watch the video.

Assessing knowledge and skills of maternity care professionals regarding neonatal hyperbilirubinaemia: a nationwide survey.

BACKGROUND: Neonatal hyperbilirubinaemia is a physiologic phenomenon, but, when severe, may cause lifelong disability. Maternity care assistants (MCAs) play an important role in timely recognition of severe neonatal jaundice. We assessed knowledge and skills of MCAs regarding neonatal hyperbilirubinaemia. METHODS: All Dutch MCAs (n = 9065) were invited to fill out a questionnaire assessing knowledge, expertise, and handling of neonatal jaundice. Additionally, we developed an e-learning and provided training sessions to a subgroup of MCAs (n = 99), and assessed their knowledge on neonatal hyperbilirubinaemia before and after the training. RESULTS: One thousand four hundred sixty-five unique online questionnaires were completed (response 16.2%). The median number of correctly answered knowledge questions was 5 (out of six; IQR 1). Knowledge was significantly better when respondents had had in-service training on neonatal hyperbilirubinaemia in the previous year (p = 0.024). Although 82% of respondents felt highly skilled or skilled to assess jaundice, accuracy of estimation of total serum bilirubin levels by assessing skin colour was generally poor and prone to underestimation. Among participants attending a training session, those who completed the e-learning beforehand had higher pre-training scores (5 (IQR 1) vs. 4 (IQR 2); p < 0.001). The median post-training score was higher than pre-training (6 (IQR 1) vs. 5 (IQR 2); p < 0.001). CONCLUSIONS: Background knowledge of MCAs regarding neonatal hyperbilirubinaemia was adequate, but can be improved by further training. Estimation of total serum bilirubin levels based on skin colour was often inadequate. Approaches to improve timely recognition of jaundiced neonates are needed.

Electronic Control of Spin-Crossover Properties in Four-Coordinate Bis(formazanate) Iron(II) Complexes.

The transition between spin states in d-block metal complexes has important ramifications for their structure and reactivity, with applications ranging from information storage materials to understanding catalytic activity of metalloenzymes. Tuning the ligand field (ΔO) by steric and/or electronic effects has provided spin-crossover compounds for several transition metals in the periodic table, but this has mostly been limited to coordinatively saturated metal centers in octahedral ligand environments. Spin-crossover complexes with low coordination numbers are much rarer. Here we report a series of four-coordinate, (pseudo)tetrahedral Fe(II) complexes with formazanate ligands and demonstrate how electronic substituent effects can be used to modulate the thermally induced transition between S = 0 and S = 2 spin states in solution. All six compounds undergo spin-crossover in solution with T1/2 above room temperature (300-368 K). While structural analysis by X-ray crystallography shows that the majority of these compounds are low-spin in the solid state (and remain unchanged upon heating), we find that packing effects can override this preference and give rise to either rigorously high-spin (6) or gradual spin-crossover behavior (5) also in the solid state. Density functional theory calculations are used to delineate the empirical trends in solution spin-crossover thermodynamics. In all cases, the stabilization of the low-spin state is due to the π-acceptor properties of the formazanate ligand, resulting in an "inverted" ligand field, with an approximate "two-over-three" splitting of the d-orbitals and a high degree of metal-ligand covalency due to metal → ligand π-backdonation. The computational data indicate that the electronic nature of the para-substituent has a different influence depending on whether it is present at the C-Ar or N-Ar rings, which is ascribed to the opposing effect on metal-ligand σ- and π-bonding.

Prognostic Factors for the Failure of Endometrial Ablation: A Systematic Review and Meta-analysis.

OBJECTIVE: To provide an overview of prognostic factors predicting failure of second-generation endometrial ablation. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched from 1988 until February 2019. The search was conducted without language restrictions using the following search terms: "endometrial ablation," "prognosis," "predict," "long term," "late onset," "outcome." METHODS OF STUDY SELECTION: The literature search provided a total of 990 studies. All types of studies reporting about prognostic factors of second-generation endometrial ablation failure were included. TABULATION, INTEGRATION, AND RESULTS: After screening for eligibility, 56 studies were included in this review, of which 21 were included in the meta-analysis. In these 56 studies, 157,830 women were included. We evaluated 10 prognostic factors: age, myomas, history of tubal ligation, body mass index, parity, preexisting dysmenorrhea, caesarean delivery, bleeding pattern, uterus position, and uterus length. Meta-analysis was performed for the primary outcome (surgical reintervention) to estimate summary treatment effects. Younger age (aged 35 years or younger, odds ratio [OR] 1.68, 95% CI 1.19-2.36; aged 40 years or younger, OR 1.58, 95% CI 1.30-1.93; aged 45 years or younger OR 1.63, 95% CI 1.28-2.07), prior tubal ligation (OR 1.46, 95% CI 1.23-1.73), and preexisting dysmenorrhea (OR 2.12, 95% CI 1.41-3.19) were associated with an increased risk of surgical reintervention. Studies investigating the prognostic factors myomas and obesity showed conflicting results. CONCLUSION: Younger age, prior tubal ligation and preexisting dysmenorrhea were found to be associated with failure of endometrial ablation. Obesity and the presence of large submucous myomas may be associated with failure, as well, though more research is necessary to estimate the influence of these factors. It is important to take the results of this review into account when counselling women with heavy menstrual bleeding. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019126247.

Independent control processes? Evidence for concurrent distractor inhibition and attentional usage of distractor information.

Interference evoked by a distractor presented prior to a target stimulus is reduced when the distractor-target SOA is increased, suggesting inhibition of distractor-related activation. Distractor processing is also assumed to be (strategically) adjusted to the proportions of congruent and incongruent target-distractor combinations, yielding a larger distractor interference effect when the proportion of congruent trials is higher (i.e., Proportion Congruent Effect, PCE). To explore the interplay of proportion congruent-based processing adjustment and the time course of distractor-related activation we varied the proportions of congruent and incongruent trials as well as the distractor-target SOA. To control for item-specific priming we kept distractor-related contingencies (i.e., frequency of individual distractor-target conjunctions) constant for a subset of the stimuli (and used a different subset to manipulate the proportions of congruent and incongruent trials). A PCE occurred, even for the subset of stimuli associated with constant distractor-related contingencies, thus ruling out item-specific contingency learning. Distractor interference was reduced when the SOA was increased, but this reduction did not differ between the proportion congruent conditions, as confirmed by a Bayesian analysis. Our results are consistent with independent processes pertaining to usage of distractor information for biasing response selection and distractor inhibition during the SOA. Alternative interpretations of the independent effects of the PC manipulation and the distractor-target SOA are discussed.

[Leg pain during menstrual period]. / Een pijnlijk been tijdens de menstruatie.

A 31-year-old woman presented at the fertility department with primary subfertility since one year. Last year she had had progressive dysmenorrhea and pain in her right leg and groin during her menstrual period. MRI showed extensive pelvic endometriosis with a lesion in the right round ligament in the inguinal canal.

Inhibition of TRPV1 prevented skin irritancy induced by phenoxyethanol. A preliminary in vitro and in vivo study.

BACKGROUND: Phenoxyethanol is a widely used preservative in personal care products. Transient receptor potential vanilloid 1 (TRPV1) on cell membrane is activated by TRPV1 agonist capsaicin resulting in an opening of the channel for calcium influx, which is linked with neurosensory sensations characterized by itching, burning and stinging of skin. Whether uncomfortable skin sensations caused by phenoxyethanol claimed by people having sensitive skin are also due to activation of TRPV1 has not been reported in the literature. OBJECTIVE: The aim of this study was to evaluate whether the TRPV1 is involved in the induction of itching and burning sensation by phenoxyethanol. METHODS AND MATERIALS: The effect of phenoxyethanol on TRPV1 was assessed in vitro on HaCaT cells. The activation of TRPV1 and its inhibition by a TRPV1 antagonist were evaluated by cellular calcium influx. TRPV1 protein expression was also investigated by Western blot. In vivo in a split-face study, phenoxyethanol formulated at 1% was compared to a formulation additionally containing a TRPV1 antagonist. By applying the formulations to the nasolabial fold, the scores of phenoxyethanol-induced sensations were compared to those of the TRPV1 antagonist. RESULTS: In vitro phenoxyethanol induced calcium influx in HaCaT cells in a dose-dependent manner after 20 min. This effect was abolished by a solution containing the TRPV1 antagonist trans-tert-butyl cyclohexanol (ID1609). Phenoxyethanol had no effect on the expression of TRPV1, whereas capsaicin caused a significant downregulation of this receptor in the same experiment. In vivo 1% phenoxyethanol induced a skin burning and itching sensation in a cohort of 60 of 243 Chinese female subjects being sensitive to phenoxyethanol discomfort. The uncomfortable skin sensations were significantly inhibited by ID1609. CONCLUSIONS: Different to capsaicin, phenoxyethanol did not downregulate the expression of TRPV1 in HaCaT cells, suggesting that different regulatory mechanisms may exist for capsaicin and phenoxyethanol. Our experiments demonstrated that phenoxyethanol induces skin misperception and uncomfortable skin sensations like itching and burning comparable to capsaicin via activating TRPV1. The stimulation was inhibited by blocking TRPV1 with ID1609. The present data strengthened hitherto studies that TRPV1 plays a critical role in sensitive skin.

RNA-binding proteins regulate cell respiration and coenzyme Q biosynthesis by post-transcriptional regulation of COQ7.

Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain carrying electrons from complexes I and II to complex III and it is an intrinsic component of the respirasome. CoQ concentration is highly regulated in cells in order to adapt the metabolism of the cell to challenges of nutrient availability and stress stimuli. At least 10 proteins have been shown to be required for CoQ biosynthesis in a multi-peptide complex and COQ7 is a central regulatory factor of this pathway. We found that the first 765 bp of the 3'-untranslated region (UTR) of COQ7 mRNA contains cis-acting elements of interaction with RNA-binding proteins (RBPs) HuR and hnRNP C1/C2. Binding of hnRNP C1/C2 to COQ7 mRNA was found to require the presence of HuR, and hnRNP C1/C2 silencing appeared to stabilize COQ7 mRNA modestly. By contrast, lowering HuR levels by silencing or depriving cells of serum destabilized and reduced the half-life of COQ7 mRNA, thereby reducing COQ7 protein and CoQ biosynthesis rate. Accordingly, HuR knockdown decreased oxygen consumption rate and mitochondrial production of ATP, and increased lactate levels. Taken together, our results indicate that a reduction in COQ7 mRNA levels by HuR depletion causes mitochondrial dysfunction and a switch toward an enhanced aerobic glycolysis, the characteristic phenotype exhibited by primary deficiency of CoQ10. Thus HuR contributes to efficient oxidative phosphorylation by regulating of CoQ10 biosynthesis.

The effect of prosthetic feedback on the strategies and synergies used by vestibular loss subjects to control stance.

BACKGROUND: This study investigated changes in stance movement strategies and muscle synergies when bilateral peripheral vestibular loss (BVL) subjects are provided feedback of pelvis sway angle. METHODS: Six BVL (all male) and 7 age-matched male healthy control (HC) subjects performed 3 stance tasks: standing feet hip width apart, eyes closed, on a firm and foam surface, and eyes open on foam. Pelvis and upper trunk movements were recorded in the roll and pitch planes. Surface EMG was recorded from pairs of antagonistic muscles at the lower leg, trunk and upper arm. Subjects were first assessed without feedback. Then, they received training with vibrotactile, auditory, and fall-warning visual feedback during stance tasks before being reassessed with feedback. RESULTS: Feedback reduced pelvis sway angle displacements to values of HCs for all tasks. Movement strategies were reduced in amplitude but not otherwise changed by feedback. These strategies were not different from those of HCs before or after use of feedback. Low frequency motion was in-phase and high frequency motion anti-phasic. Feedback reduced amplitudes of EMG, activity ratios (synergies) of antagonistic muscle pairs and slightly reduced baseline muscle activity. CONCLUSIONS: This is the first study demonstrating how vestibular loss subjects achieve a reduction of sway during stance with prosthetic feedback. Unchanged movement strategies with reduced amplitudes are achieved with improved antagonistic muscle synergies. This study suggests that both body movement and muscle measures could be explored when choosing feedback variables, feedback location, and patient groups for prosthetic devices which reduce sway of those with a tendency to fall.

miR-127-5p targets the 3'UTR of human ß-F1-ATPase mRNA and inhibits its translation.

The mitochondrial H(+)-ATP synthase is a bottleneck component in the provision of metabolic energy by oxidative phosphorylation. The expression of its catalytic subunit (ß-F1-ATPase) is stringently controlled at post-transcriptional levels during oncogenesis, the cell cycle and in development. Here we show that miR-127-5p targets the 3'UTR of ß-F1-ATPase mRNA (ß-mRNA) significantly reducing its translational efficiency without affecting ß-mRNA abundance. Despite the reduced expression of ß-F1-ATPase in most human carcinomas, we observed no expression of miR-127-5p in different human cancer cell lines, minimizing the potential role of miR-127-5p as a regulator of the bioenergetic activity of mitochondria in cancer. In contrast, miR-127-5p is highly over-expressed in the human fetal liver. Consistent with previous findings in the rat, the expression of ß-F1-ATPase in the human liver also seems to be controlled at post-transcriptional levels during development, what might suggest a role for miR-127-5p in controlling ß-mRNA translation and thus in defining the bioenergetic activity of human liver mitochondria. Moreover, immunolocalization techniques and subcellular fractionation experiments using different antibodies against ß-F1-ATPase reveal that the ectopic expression of ß-F1-ATPase at the cell surface of the hepatocytes and HepG2 cells is negligible or stands for scrutiny.

Post-transcriptional regulation of the mitochondrial H(+)-ATP synthase: a key regulator of the metabolic phenotype in cancer.

A distinctive metabolic trait of tumors is their enforced aerobic glycolysis. This phenotype was first reported by Otto Warburg, who suggested that the increased glucose consumption of cancer cells under aerobic conditions might result from an impaired bioenergetic activity of their mitochondria. A central player in defining the bioenergetic activity of the cell is the mitochondrial H(+)-ATP synthase. The expression of its catalytic subunit ß-F1-ATPase is tightly regulated at post-transcriptional levels during mammalian development and in the cell cycle. Moreover, the down-regulation of ß-F1-ATPase is a hallmark of most human carcinomas. In this review we summarize our present understanding of the molecular mechanisms that participate in promoting the "abnormal" aerobic glycolysis of prevalent human carcinomas. The role of the ATPase Inhibitor Factor 1 (IF1) and of Ras-GAP SH3 binding protein 1 (G3BP1), controlling the activity of the H(+)-ATP synthase and the translation of ß-F1-ATPase mRNA respectively in cancer cells is emphasized. Furthermore, we underline the role of mitochondrial dysfunction as a pivotal player of tumorigenesis.

Human G3BP1 interacts with beta-F1-ATPase mRNA and inhibits its translation.

The post-transcriptional regulation of nuclear mRNAs that encode core components of mitochondria has relevant implications in cell physiology. The mRNA that encodes the catalytic subunit of the mitochondrial H(+)-ATP synthase subunit beta (ATP5B, beta-F1-ATPase) is localized in a large ribonucleoprotein (RNP) complex (beta-F1-RNP), which is subjected to stringent translational control during development and the cell cycle, and in carcinogenesis. Because downregulation of beta-F1-ATPase is a conserved feature of most prevalent human carcinomas, we have investigated the molecular composition of the human beta-F1-RNP. By means of an improved affinity-chromatography procedure and protein sequencing we have identified nine RNA-binding proteins (RNABPs) of the beta-F1-RNP. Immunoprecipitation assays of Ras-GAP SH3 binding protein 1 (G3BP1) and fluorescent in-situ hybridization of mRNA indicate a direct interaction of the endogenous G3BP1 with mRNA of beta-F1-ATPase (beta-F1 mRNA). RNA-bridged trimolecular fluorescence complementation (TriFC) assays confirm the interaction of G3BP1 with the 3'-UTR of beta-F1 mRNA in cytoplasmic RNA-granules. Confocal and high-resolution immunoelectron-microscopy experiments suggest that the beta-F1-RNP is sorted to the periphery of mitochondria. Molecular and functional studies indicate that the interaction of G3BP1 with beta-F1 mRNA inhibits its translation at the initiation level, supporting a role for G3BP1 in the glycolytic switch that occurs in cancer.