Cell Biology

Not Death-Defying

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Science  03 Jun 2011:
Vol. 332, Issue 6034, pp. 1129
DOI: 10.1126/science.332.6034.1129-a
CREDIT: ALBERT HERMS

Caveolae are membrane invaginations found at the surface of mammalian cells that are enriched in cholesterol. Cholesterol-binding proteins known as caveolins play a key role in caveolar formation and are also involved in intracellular cholesterol transport. Mutation or disruption of caveolin genes have been linked to a variety of pathologies, including lipodystrophy, cardiovascular disease, diabetes, and cancer. Bosch et al. examined the cellular pathology associated with caveolin disruption in embryonic fibroblast cells from caveolin 1 (CAV1)–deficient mice. The cells exhibited reduced proliferation and survival when subjected to glucose restriction—a phenotype associated with compromised mitochondria. Indeed, mitochondrial membranes from the CAV1-deficient cells contained elevated levels of free cholesterol, which was associated with reduced resistance to antioxidants. The mitochondria thus accumulated reactive oxygen species, which promoted cell death. Thus, mitochondrial dysfunction appears to be the underlying cause of the variety of pathologies observed in CAV1-deficient animals.

Curr. Biol. 21, 681 (2011).

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