Death and the shrinking nucleus

During heart disease and stroke, cells deprived of oxygen often die in a way that is distinct from caspase-dependent apoptosis. On page 1219, Shinzawa and Tsujimoto provide a first look at the molecular basis of this poorly understood process, showing that a phospholipase A₂ (PLA₂) enzyme causes the characteristic nuclear shrinkage that accompanies hypoxic cell death.

Using a novel permeabilized cell assay, the authors purified a protein that can cause nuclear shrinkage and identified it as PLA₂. Inhibitor studies confirmed that PLA₂ is essential for nuclear shrinkage in caspase-independent hypoxic cell death. In hypoxic cells, PLA₂ activity increases and the calcium-independent form of the enzyme accumulates in the nucleus. Blocking calcium-independent PLA₂ activity prevents both nuclear shrinkage and hypoxic cell death.

An increase in PLA₂ activity leads...