Mitochondria and lysosomes are functionally linked, and their interdependent decline is a hallmark of aging and disease. Despite the long-standing connection between these organelles, the function(s) of lysosomes required to sustain mitochondrial health remains unclear. Here, working in yeast, we show that the lysosome-like vacuole maintains mitochondrial respiration by spatially compartmentalizing amino acids. Defects in vacuole function result in a breakdown in intracellular amino acid homeostasis, which drives age-related mitochondrial decline. Among amino acids, we find that cysteine is most toxic for mitochondria and show that elevated non-vacuolar cysteine impairs mitochondrial respiration by limiting intracellular iron availability through an oxidant-based mechanism. Cysteine depletion or iron supplementation restores mitochondrial health in vacuole-impaired cells and prevents mitochondrial decline during aging. These results demonstrate that cysteine toxicity is a major driver of age-related mitochondrial deterioration and identify vacuolar amino acid compartmentation as a cellular strategy to minimize amino acid toxicity.
The first blast furnace in Britain was recorded in 1496, and they spread across the country during the 1550s. The blast furnaces made pig iron from iron ore, and the basic principle was similar to that of the bloomery, using charcoal, but the smelting temperature was higher. Water was used to drive the bellows to create the draught. Later, in 1709, Abraham Darby used coal/coke as a fuel at his Coalbrookdale (the Midlands) furnaces and, within 100 years, the use of coke was almost universal.
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From the 1770s until 1789, the Iron Mill at Funtley was owned by Henry Cort, the inventor of the rolling mill and the puddling furnace, important for the production of iron during the Napoleonic Wars.
As a young man, Cort was a supplier of naval provisions and by the 1770s he had built himself a small fortune. In 1768, he married Elizabeth Heysham, whose uncle William had inherited the family ironmongery business in Gosport, which supplied the navy with mooring chains, anchors and hundreds of different items of ironmongery. Henry took over the business and, after years of experimenting with improved methods for wrought-iron production, in 1775 he bought a forge and slitting mill at Funtley. He wanted to continue his experiments, hoping to find an easier way to turn cast iron into wrought iron without the need for hammering.
Because the puddling method used coal/coke instead of expensive charcoal, and because the system could be mechanised, eventually iron production became much cheaper and faster. It also became essential once blast furnaces were used. Before Henry developed his processes, England imported large quantities of wrought iron from abroad, but within a decade of his patents, the country became a major iron exporter.
Born at Merthyr Tydfil. He received his early training in the Cyfarthfa iron-works. After experience in Ebbw Vale works and in Newport he was appointed general manager of the Millwall Docks iron-works, Thames, London. There he gained a reputation, which extended as far as Russia, for discovering improved methods of producing steel. Russia lacked railways, and her industries had not been developed; the country had also to import steel and iron from the Merthyr and Dowlais districts at great expense. To avoid this, she decided to develop her own industries and John Hughes was invited to establish works in Russia.
He was allowed to select any suitable site, but after journeyings throughout the length and breadth of the land, he decided to settle in the Donetz basin, at a lonely spot on the Steppes; but some distance away were the great iron-ore mines of Krivirog and the port of Taganrog. John Hughes formed the New Russia Company in 1869 and within a few years a large town was built for the workmen, which was called Hughesoffka after his name. He induced a considerable number of iron-workers from Merthyr, Dowlais, Rhymney, and Middlesbrough to accompany him. The works flourished and became the centre of the great industrial district of the Don Basin. ff782bc1db
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