Membrane-enclosed organelles, a defining characteristic of eukaryotic
cells, are lost during differentiation of specific cell types such as
reticulocytes (an intermediate in differentiation of erythrocytes), ce
ntral fibre cells of the eye lens, and keratinocytes(1). The degradati
on of these organelles must be tightly regulated with respect to both
the time of activation and the specificity of membrane degradation. Th
e expression of 15-lipoxygenase (15-LOX) peaks in reticulocytes immedi
ately before organelle degradation(2). Here we show that 15-LOX integr
ates into the membranes of various organelles, allowing release of pro
teins from the organelle lumen and access of proteases to both lumenal
and integral membrane proteins. In addition, by sparing the plasma me
mbrane, 15-LOX shows the required specificity for organellar membranes
. Thus, the action of 15-LOX provides a mechanism by which the natural
degradation process can be explained. This conclusion is supported by
our finding that lipoxygenase expression in the eye lens is restricte
d to the region at which organelle degradation occurs.