Medical Research Council - London Institute of Medical Sciences

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Partial Breakdown

Insight into how cells regulate cholesterol - levels are high when oxygen is low

28 February 2023

Partial Breakdown

Like too much of a good thing, high levels of cholesterol, an essential component of cell membranes, are linked to multiple health problems; pictured are cholesterol crystals in joint or synovial fluid, a symptom associated with diseases like gout. To maintain a healthier balance, cells slow down cholesterol production when it becomes too abundant, by breaking down a key enzyme involved in making cholesterol, squalene monooxygenase (SM). Yet when cells experience low oxygen levels, or hypoxia, this process fails: SM is only partially broken down, leaving a shortened version that remains active, and so keeping cholesterol levels high. Making cholesterol is an oxygen-hungry process, requiring eleven molecules of oxygen for each cholesterol produced, so preserving SM activity when oxygen is low might help cells cope with fluctuations in oxygen. Conversely, interfering with this partial breakdown of SM could potentially be a winning strategy for treatments aiming to bring cholesterol down.

Written by Emmanuelle Briolat

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