scholarly journals Decision letter: Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome

2019 ◽  
Author(s):  
Johannes M Herrmann
Keyword(s):  
Neuronal Cells ◽  
Complex Iv ◽  
Insight Into

scholarly journals Author response: Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome

2019 ◽  
Author(s):  
Yilin Kang ◽  
Alexander J Anderson ◽  
Thomas Daniel Jackson ◽  
Catherine S Palmer ◽  
David P De Souza ◽  
...  
Keyword(s):  
Response Function ◽  
Neuronal Cells ◽  
Author Response ◽  
Complex Iv ◽  
Insight Into

scholarly journals Author response: Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome

2019 ◽  
Author(s):  
Yilin Kang ◽  
Alexander J Anderson ◽  
Thomas Daniel Jackson ◽  
Catherine S Palmer ◽  
David P De Souza ◽  
...  
Keyword(s):  
Response Function ◽  
Neuronal Cells ◽  
Author Response ◽  
Complex Iv ◽  
Insight Into

scholarly journals Correction: Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yilin Kang ◽  
Alexander J Anderson ◽  
Thomas Daniel Jackson ◽  
Catherine S Palmer ◽  
David P De Souza ◽  
...  
Keyword(s):  
Neuronal Cells ◽  
Correction Function ◽  
Complex Iv ◽  
Insight Into

scholarly journals Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Yilin Kang ◽  
Alexander J Anderson ◽  
Thomas Daniel Jackson ◽  
Catherine S Palmer ◽  
David P De Souza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disease ◽  
Neuronal Cells ◽  
Underlying Mechanism ◽  
Copper Chaperone ◽  
Intermembrane Space ◽  
Complex Iv ◽  
Enhanced Sensitivity ◽  
Chaperone Network ◽  
Insight Into

Human Tim8a and Tim8b are members of an intermembrane space chaperone network, known as the small TIM family. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells or how mutation of this protein leads to a neurodegenerative disease. We show that hTim8a is required for the assembly of Complex IV in neurons, which is mediated through a transient interaction with Complex IV assembly factors, in particular the copper chaperone COX17. Complex IV assembly defects resulting from loss of hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c, which primes cells for death. Alleviation of oxidative stress with Vitamin E treatment rescues cells from apoptotic vulnerability. We hypothesise that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.

scholarly journals Neuronal-specific function of hTim8a in Complex IV assembly provides insight into the molecular mechanism underlying Mohr-Tranebjærg syndrome

2019 ◽  
Author(s):  
Yilin Kang ◽  
Alexander J. Anderson ◽  
David P. De Souza ◽  
Catherine S. Palmer ◽  
Kenji M. Fujihara ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disease ◽  
Neuronal Cells ◽  
Underlying Mechanism ◽  
Copper Chaperone ◽  
Intermembrane Space ◽  
Specific Function ◽  
Hydrophobic Membrane ◽  
Complex Iv ◽  
Enhanced Sensitivity

AbstractHuman Tim8a is a member of an intermembrane space chaperone network, known as the small TIM family, which transport hydrophobic membrane proteins through this compartment. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells and consequently how lack of hTim8a leads to a neurodegenerative disease. We identified a novel cell-specific function of hTim8a in the assembly of Complex IV, which is mediated through a transient interaction with the copper chaperone COX17. Complex IV assembly defects in cells lacking hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c and Bax, which primes cells for cell death. Alleviation of oxidative stress using Vitamin E rescues cells from apoptotic vulnerability. We hypothesis that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.

scholarly journals Lower oxidative DNA damage despite greater ROS production in muscles from rats selectively bred for high running capacity

2011 ◽  
Vol 300 (3) ◽  
pp. R544-R553 ◽  
Author(s):  
Constance Tweedie ◽  
Caroline Romestaing ◽  
Yan Burelle ◽  
Adeel Safdar ◽  
Mark A. Tarnopolsky ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Citrate Synthase ◽  
Disease Risk ◽  
High Capacity ◽  
Oxygen Metabolism ◽  
Antioxidant Enzyme Activities ◽  
Complex Iv ◽  
Activity Marker ◽  
Insight Into

Artificial selection in rat has yielded high-capacity runners (HCR) and low-capacity runners (LCR) that differ in intrinsic (untrained) aerobic exercise ability and metabolic disease risk. To gain insight into how oxygen metabolism may have been affected by selection, we compared mitochondrial function, oxidative DNA damage (8-dihydroxy-guanosine; 8dOHG), and antioxidant enzyme activities in soleus muscle (Sol) and gastrocnemius muscle (Gas) of adult and aged LCR vs. HCR rats. In Sol of adult HCR rats, maximal ADP-stimulated respiration was 37% greater, whereas in Gas of adult HCR rats, there was a 23% greater complex IV-driven respiratory capacity and 54% greater leak as a fraction of electron transport capacity (suggesting looser mitochondrial coupling) vs. LCR rats. H2O2 emission per gram of muscle was 24–26% greater for both muscles in adult HCR rats vs. LCR, although H2O2 emission in Gas was 17% lower in HCR, after normalizing for citrate synthase activity (marker of mitochondrial content). Despite greater H2O2 emission, 8dOHG levels were 62–78% lower in HCR rats due to 62–96% higher superoxide dismutase activity in both muscles and 47% higher catalase activity in Sol muscle in adult HCR rats, with no evidence for higher 8 oxoguanine glycosylase (OGG1; DNA repair enzyme) protein expression. We conclude that genetic segregation for high running capacity has generated a molecular network of cellular adaptations, facilitating a superior response to oxidative stress.

Calibration problems in hydrogen luminosities

1966 ◽  
Vol 24 ◽  
pp. 322-330
Author(s):  
A. Beer
Keyword(s):  
Galactic Structure ◽  
B Stars ◽  
Insight Into

The investigations which I should like to summarize in this paper concern recent photo-electric luminosity determinations of O and B stars. Their final aim has been the derivation of new stellar distances, and some insight into certain patterns of galactic structure.

Stochasting modeling of planetary ring systems

1984 ◽  
Vol 75 ◽  
pp. 461-469 ◽  
Author(s):  
Robert W. Hart
Keyword(s):  
Maximum Entropy ◽  
Ring System ◽  
The Sun ◽  
Ultimate State ◽  
Interparticle Interactions ◽  
Ring Systems ◽  
First Order ◽  
Planetary Ring ◽  
Insight Into

ABSTRACTThis paper models maximum entropy configurations of idealized gravitational ring systems. Such configurations are of interest because systems generally evolve toward an ultimate state of maximum randomness. For simplicity, attention is confined to ultimate states for which interparticle interactions are no longer of first order importance. The planets, in their orbits about the sun, are one example of such a ring system. The extent to which the present approximation yields insight into ring systems such as Saturn's is explored briefly.

Skeletal elements of crinoid echinoderms: High-resolution structural and microanalytical results

1983 ◽  
Vol 41 ◽  
pp. 194-195
Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor
Keyword(s):  
High Resolution ◽  
Marine Invertebrates ◽  
Sea Urchins ◽  
Structural Features ◽  
Sea Stars ◽  
High Resolution Tem ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.

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