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Scientists uncover SREBP-2 role in autophagy and cholesterol generation

March 14, 2016

When times get tough, autophagy is the cell's way of recycling its own old or damaged parts. Dr. Osborne and his team found that SREBP-2 uses autophagy as a way to liberate cholesterol stored by some cells in fat droplets. (Here they looked at liver cells, which have large fat droplets. In contrast, other cell types - neurons, for example - aren't known to store fat.) When cholesterol was limited, autophagy genes were switched on and fat droplets were joined by autophagosomes (bags of enzymes the cell deploys for self-destruction). As a result, more cholesterol was available for cells to repair membranes, burn as energy or drive other life-sustaining processes.

The role of SREBP-2 in autophagy and cholesterol generation was confirmed using cells engineered to lack the protein. Facing cholesterol shortage, SREBP-2-deficient cells were unable to switch on autophagy genes and autophagosomes did not form as readily as they did in normal cells.

"This study identified a key regulatory step that determines how cells decide whether they have sufficient stored fat, or whether new fat needs to be produced internal cellular sources or obtained from the environment," Dr. Osborne said. "Genetic or environmental conditions that interfere with this regulatory step could lead to diseases such as obesity or cardiovascular disease."

Source: Sanford-Burnham Medical Research Institute