427 research outputs found
Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery
Saccharomyces cerevisiae Mdm38 and Ylh47 are homologues of human Letm1, a protein implicated in Wolf-Hirschhorn syndrome. We analyzed the function of Mdm38 and Ylh47 in yeast mitochondria to gain insight into the role of Letm1. We find that mdm38Δ mitochondria have reduced amounts of certain mitochondrially encoded proteins and low levels of complex III and IV and accumulate unassembled Atp6 of complex V of the respiratory chain. Mdm38 is especially required for efficient transport of Atp6 and cytochrome b across the inner membrane, whereas Ylh47 plays a minor role in this process. Both Mdm38 and Ylh47 form stable complexes with mitochondrial ribosomes, similar to what has been reported for Oxa1, a central component of the mitochondrial export machinery. Our results indicate that Mdm38 functions as a component of an Oxa1-independent insertion machinery in the inner membrane and that Mdm38 plays a critical role in the biogenesis of the respiratory chain by coupling ribosome function to protein transport across the inner membrane
The Role of Glutamate and GABA in Autism Spectrum Disorders: Pilot Results from a Proton Magnetic Resonance Spectroscopy Study
Objectives: To measure the levels of glutamate, a major excitatory neurotransmitter; glutamine, a metabolite of glutamate; and γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter; in a pilot study of proton magnetic resonance spectroscopy (1H-MRS) findings in adolescents with Autism Spectrum Disorders (ASD).
Methods: The subjects were assessed with the Autism Diagnostic Observation Schedule (ADOS), the Reading the Mind in the Eyes test (RMET) and the Social Responsiveness Scale (SRS). 1H-MRS measures of the anterior cingulate cortex were conducted using a Philips 3.0 T scanner.
Results: To date, we have completed the data analysis on 18 subjects, 8 with ASD and 10 healthy control (HC) subjects. There was no significant difference between the combined glutamate + glutamine concentrations as measured by 1H-MRS (ASD = 12.0 ± 0.9 IU, HC = 11.6 ± 0.8 IU, p = 0.37). However, there was a higher than average glutamine level in the ASD group compared to healthy controls (ASD = 2.4 ± 0.2 IU, HC = 1.9 ± 0.3 IU, p = 0.01). This was accompanied by a trend toward lower GABA/Cr levels in the ASD group (ASD = 0.073 ± 0.010, HC = 0.082 ± 0.010, p = 0.06). Glutamine levels in the ACC were correlated positively with deficits of social cognition across groups (higher SRS, lower RMET scores). Those with higher glutamine levels made more errors when identifying emotions in the RMET task (r(10) = -0.77, p = 0.009), and also had more clinically significant scores on the SRS (r(10) = 0.87, p = 0.001).
Conclusions: Our results present evidence that glutamine levels measured within the ACC region are higher for adolescent males with ASD than age-matched HC males, and signal that GABA levels may also be decreased in this region. These changes are correlated with deficits in social cognition
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A J-protein is an essential subunit of the presequence translocase–associated protein import motor of mitochondria
Transport of preproteins into the mitochondrial matrix is mediated by the presequence translocase–associated motor (PAM). Three essential subunits of the motor are known: mitochondrial Hsp70 (mtHsp70); the peripheral membrane protein Tim44; and the nucleotide exchange factor Mge1. We have identified the fourth essential subunit of the PAM, an essential inner membrane protein of 18 kD with a J-domain that stimulates the ATPase activity of mtHsp70. The novel J-protein (encoded by PAM18/YLR008c/TIM14) is required for the interaction of mtHsp70 with Tim44 and protein translocation into the matrix. We conclude that the reaction cycle of the PAM of mitochondria involves an essential J-protein
ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism
Girls and Boys Born before 28Â Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10Â Years
To compare the prevalence of cognitive, neurological, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm (EP)
DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer
Ann Killary and colleagues describe a new gene that is genetically altered in breast tumors, and that may provide a new breast cancer prognostic marker
Neuronal and astrocyte dysfunction diverges from embryonic fibroblasts in the Ndufs4fky/fky mouse
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