Perhaps the question is not why aggregates are formed in disease, but why they do not form in healthy cells. “One of the things I often ask in group meetings is: Why are the eggs not given to the cell?” Hyman spoke at the cell biology meeting; The protein content of the cytoplasm is “so concentrated that it should only crash out of solution.”
A clue was found when researchers at Hyman’s lab added cellular fuel ATP to the condensation of pure fuel granule proteins and saw those condensates disappear. For further investigation, the researchers poured egg albumin into a test tube, mixed ATP with salt in one tube and another, and then heated them. While egg whites tend to collect, ATP ones were not: ATP was inhibiting protein aggregation at concentrations found in living cells.
but how? This remained an enigma until Hyman met a chemist while presenting a seminar in Bangalore. The chemist stated that in industrial processes, an additive called hydrophobic is used to increase the solubility of hydrophobic molecules. Returning to their laboratory, Hyman and his colleagues found that ATP worked exceptionally well as a hydrotrop.
Intuitively, ATP is a very abundant metabolite in cells, with a specific concentration of 3–5 mM. Most enzymes that use ATP operate efficiently with low concentrations of three. Why, then, is ATP so concentrated inside cells, if it is not required to drive metabolic reactions?
One candidate explanation, Hyman suggests, is that ATP does not act as a hydrotrop below 3-5 millimeters. “One possibility is that at the origin of life, ATP may have evolved as biological concentrations to keep the bio-concentrations soluble at high concentrations and subsequently co-opted as energy.”
This hypothesis is difficult to test that experimentally, Hyman accepts, because it is challenging to manipulate the hydrotropic properties of ATP without affecting its energy function. But if this idea is correct, it may help explain why protein is commonly formed in diseases associated with aging, as ATP production becomes effective only at an early age.
Other uses for drops
Protein aggregates are clearly impaired in neurodegenerative diseases. But the transition from liquid to solid phases can be adaptive under other circumstances.
Take primordial ococytes, cells in the ovary that can lie dormant for decades before maturing into an egg. Each of these cells has a Balinese body, a large condensate of amyloid proteins found in oocytes of organisms ranging from spiders to humans. The Balinese body is believed to protect mitochondria during the dormant phase of the oocyte. Clustering together most of the mitochondria With prolonged amyloid protein fibers. When the oocyte begins to mature in an egg, those amyloid fibers are dissolved and the Balinese body disappears, explains Elvan Böke, a cell and developmental biologist at the Center for Genomic Regulations in Barcelona. Boeck is working to understand how these amyloid fibers collect and dissolve, which may lead to new strategies for treating infertility or neurodegenerative diseases.
Protein aggregates can also solve problems that require very quick physical responses, such as stopping bleeding after injury. for example, Mucor Circinelloides There is a fungal species through a network of interconnected pressures of the root-like hypahite, through which nutrients flow. Researchers at the Temasek Life Sciences Laboratory recently led the evolutionary cell biologist Greg Z. Discovered That when they injured the tip of one Mukker The hype, protoplasm already ejected but almost immediately formed a gelatinous plug that stopped the bleeding.
Jade doubted that this reaction was mediated by a long polymer, perhaps a protein with a repetitive structure. Researchers identified two candidate proteins and found that, without them, the fungal-injured fungus exploded into a puddle of protoplasm.