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bioRxiv · 10.1101/2021.12.02.471013

ABCA1 causes an asymmetric cholesterol distribution to regulate intracellular cholesterol homeostasis

Ogasawara, F.·Ueda, K.
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Abstract

Cholesterol is a major and essential component of the mammalian cell plasma membrane (PM) and the loss of cholesterol homeostasis leads to various pathologies. Cellular cholesterol uptake and synthesis are regulated by a cholesterol sensor in the endoplasmic reticulum (ER). However, it remains unclear how the PM cholesterol level is sensed. Here we show that the sensing depends on ATP-binding cassette A1 (ABCA1) and Aster-A, which cooperatively maintain the asymmetric transbilayer cholesterol distribution in the PM. ABCA1 translocates (flops) cholesterol from the inner to the outer leaflet of the PM to maintain a low inner cholesterol level. When the inner cholesterol level exceeds a threshold, Aster-A is recruited to the PM-ER contact site to transfer cholesterol to the ER. These results show unknown synergy between ABCA1 and Aster-A in intracellular cholesterol homeostasis.

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Ogasawara, F., Ueda, K.. 2021-12-03. ABCA1 causes an asymmetric cholesterol distribution to regulate intracellular cholesterol homeostasis. https://doi.org/10.1101/2021.12.02.471013

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