E3 Ligase Subunit Fbxo15 and PINK1 Kinase Regulate Cardiolipin Synthase 1 Stability and Mitochondrial Function in Pneumonia

Acute lung injury (ALI) is linked to mitochondrial injury, resulting in impaired cellular oxygen utilization; however, it is unknown how these events are linked on the molecular level. Cardiolipin, a mitochondrial-specific lipid, is generated by cardiolipin synthase (CLS1). Here, we show that S.aureus activates a ubiquitin E3 ligase component, Fbxo15, that is sufficient to mediate proteasomal degradation of CLS1 in epithelia, resulting in decreased cardiolipin availability and disrupted mitochondrial function. CLS1 is destabilized by the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1), which binds CLS1 to phosphorylate and regulates CLS1 disposal. Like Fbxo15, PINK1 interacts with and regulates levels of CLS1 through a mechanism dependent upon Thr219. S.aureus infection upregulates this Fbxo15-PINK1 pathway to impair mitochondrial integrity, and Pink1 knockout mice are less prone to S.aureus-induced ALI. Thus, ALI-associated disruption of cellular bioenergetics involves bioeffectors that utilize a phosphodegron to elicit ubiquitin-mediated disposal of a key mitochondrial enzyme. © 2014 The Authors

Phosphorus:Reserves, production, and applications

The demand of phosphate fertilizers is growing as a result of a rising population, changing human diets resulting in the increasing (meat) consumption per capita, and an expansion in the production of biofuels. Besides the fertilizer industry, there is a steady growth of using phosphorus compounds in the chemical industry for applications in, e.g., soft drinks, pharmaceuticals, and flame retardants. To meet this growth, it is important to know if the P reserves are sufficient and what kind of processes are used to produce such phosphorus compounds. Reserves are not equally spread around the world, with three-quarters located in Morocco and The Western Sahara. Prices can be volatile, as shown in 2008 with an eightfold price increase. Moreover, the estimated time till depletion of phosphate rock differs substantially between several studies. Therefore, phosphate rock was added on the critical material list of the European Commission. An important aspect for the processing of phosphate rock is the quality of the rock, which is dependent on the ore type (sedimentary or igneous), level of radioactivity, and hazardous metal contents. The main intermediary compounds for phosphorus products are phosphoric acid and white phosphorus. About 95% of the phosphoric acid is made via the wet process: acidulation of phosphate rock to create wet phosphoric acid and the main by-products phosphogypsum and hydrogen fluoride. The purity and thus the reusability of phosphogypsum are dependent on the type of digestion process. However, at the moment, reusing phosphogypsum is not a common practice. Wet phosphoric acid can be purified via several processes. The most common processes are extraction and precipitation. Via extraction, wet phosphoric acid can be purified up to phosphoric acid comparable to that produced with the thermal process. Separation of specific compounds can be done through precipitation. Additionally, cationic impurities can be removed via precipitation, but the product will then be changed into a phosphate salt, which is unfavorable for its use in industrial applications