Indentor-escape, delamination and orogenic collapse of the ca. 600-500 Ma East African/Antarctic Orogen in Mozambique and Dronning Maud Land (East Antarctica)

The East African/Antarctic Orogen (EAAO) is one of the largest orogenic belts on the planet, resulting from the collision of various parts of East and West- Protogondwana between ca. 600 and 550 Ma. The central and southern parts of the orogen are typified by high-grade rocks, representing the overprinted margins of the various colliding continental blocks. New fieldwork and geochronology in northern Mozambique reveals a protracted polyphase Ediacaran/Cambrian deformation history. New age constraints reveal high-grade metamorphism at 600-550 Ma, overprinting and older basement

Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology

Plants and many lower organisms, but not mammals, express alternative oxidases (AOXs) that branch the mitochondrial respiratory chain, transferring electrons directly from ubiquinol to oxygen without proton pumping. Thus, they maintain electron flow under conditions when the classical respiratory chain is impaired, limiting excess production of oxygen radicals and supporting redox and metabolic homeostasis. AOX from Ciona intestinalis has been used to study and mitigate mitochondrial impairments in mammalian cell lines, Drosophila disease models and, most recently, in the mouse, where multiple lentivector-AOX transgenes conferred substantial expression in specific tissues. Here, we describe a genetically tractable mouse model in which Ciona AOX has been targeted to the Rosa26 locus for ubiquitous expression. The AOX(Rosa26) mouse exhibited only subtle phenotypic effects on respiratory complex formation, oxygen consumption or the global metabolome, and showed an essentially normal physiology. AOX conferred robust resistance to inhibitors of the respiratory chain in organello; moreover, animals exposed to a systemically applied LD50 dose of cyanide did not succumb. The AOX(Rosa26) mouse is a useful tool to investigate respiratory control mechanisms and to decipher mitochondrial disease aetiology in vivo.Peer reviewe

Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

Abstract Cardiac ischaemia-reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re-perfused post-ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post-anoxic heart mitochondria. However, post-ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up-regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro-fibrotic and pro-apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label-free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC-derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.Peer reviewe

Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

Abstract Cardiac ischaemia-reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re-perfused post-ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post-anoxic heart mitochondria. However, post-ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up-regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro-fibrotic and pro-apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label-free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC-derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.Peer reviewe

Coupled delamination and indentor-escape tectonics in the southern part of the c. 650-500 Ma East African/Antarctic Orogen

The East African/Antarctic Orogen (EAAO) is one of the largest orogenic belts on the planet, resulting from the collision of various parts of East and West- Protogondwana between 620 and 550 Ma. The central and southern parts of the orogen are typified by high-grade rocks, representing the overprinted margins of the various colliding continental blocks. The southern third of this Himalayan-type orogen can be interpreted in terms of a lateral tectonic escape model, similar to the situation presently developing in SE-Asia. One of the escape-related shear zones of the EAAO is exposed as the approximately 20 km wide Heimefront transpression zone in western Dronning Maud Land (Antarctica). During Gondwana break-up, the southern part of the EAAO broke up into a number of microplates (Falkland, Ellsworth-Haag and Filchner blocks). These microplates probably represent shear zone-bound blocks, which were segmented by tectonic translation during lateral tectonic extrusion. The southern part of the EAAO is also typified by large volumes of late-tectonic A2-type granitoids that intruded at c. 530-490 Ma, and can constitute up to 50% of the exposed basement. They are likely the consequence of delamination of the orogenic root and the subsequent influx of hot asthenospheric mantle during tectonic escape. The intrusion of these voluminous melts into the lower crust was accompanied by orogenic collapse. The A2-type magmatism appears to terminate along the Lurio Belt in northern Mozambique. Therefore, the Lurio Belt could represent an accommodation zone, separating an area to the south in which the orogen underwent delamination of the orogenic root, and an area to the north, where the orogenic keel is still present. Erosional unroofing of the northern EAAO is documented by the remnants of originally extensive areas covered by Cambro- Ordovician molasse-type clastic sedimentary rocks throughout North Africa and Arabia, testifying to the size of this megaorogen. Whilst the EAAO molasse in the north covers almost the entire North African platform, probably resulting from a long lasting high standing mountain range (no delaminated root), the molasse deposits of the southern EAAO are comparatively smaller, possibly resulting from the rapid and mechanical thinning of the orogen in the south (delaminated root)

TRPM4

TRPM4 is a Ca(2+)-activated nonselective cation channel. The channel is activated by an increase of intracellular Ca(2+) and is regulated by several factors including temperature and Pi(4,5)P2. TRPM4 allows Na(+) entry into the cell upon activation, but is completely impermeable to Ca(2+). Unlike TRPM5, its closest relative in the transient receptor potential family, TRPM4 proteins are widely expressed in the body. Currents with properties that are reminiscent of TRPM4 have been described in a variety of tissues since the advent of the patch clamp technology, but their physiological role is only beginning to be clarified with the increasing characterization of knockout mouse models for TRPM4. Furthermore, mutations in the TRPM4 gene have been associated with cardiac conduction disorders in human patients. This review aims to overview the currently available data on the functional properties of TRPM4 and the current understanding of its physiological role in healthy and diseased tissue.status: publishe

Structural evolution of Dronning Maud Land (East Antarctica) and significance for links with the East African and Kuunga orogens

In Dronning Maud Land (DML), East Antarctica, a ca. 620-500 Ma mobile belt dissects the continent. This ca. 1000 km wide orogen has been linked to the East African Orogen on the one hand and relationships to the Kuunga orogen were suggested on the other. The mobile belt reworks mainly Grenville-age crust. The foreland hinterland boundaries are clearly defined in the Heimefrontjella (western DML) and in eastern DML (Sor Rondane), both as major dextral transpression zones. The mobile belt is characterized by medium to high-grade metamorphism between ca. 620 - 500 Ma