Cholesterol availability drives the assembly of mitochondria-associated ER membranes

Increased plasma membrane cholesterol availability promotes the assembly of mitochondria-associated ER membranes (MAM domains), with HDL/SR-B1–mediated cholesterol redistribution rapidly increasing MAM formation.

• Why it matters: MAM domains coordinate ER–mitochondria metabolic signaling, but how extracellular cholesterol availability is translated into MAM assembly is not well defined.
• What they did: Cells were exposed to HDL cholesterol delivered through the SR-B1 pathway, tracking rapid cholesterol redistribution from the plasma membrane to the ER and measuring resulting MAM domain assembly.
• The result: Higher MAM formation enhances ER–mitochondria communication, increases cholesterol esterification, and suppresses cholesterol biosynthesis; disrupting MAMs uncouples these responses and alters metabolic adaptation to extracellular cholesterol.

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