Phosphatidylserine translocation in animal cells.

The metabolism of phosphatidylserine to phosphatidylethanolamine by cultured animal cells provides a useful system for studying one of the mechanisms of lipid translocation among subcellular organelles. The translocation dependent decarboxylation of phosphatidylserine can be significantly inhibited by depleting cellular ATP levels with metabolic poisons. Poisoned cells not only fail to decarboxylate nascent phosphatidylserine but also accumulate this lipid in the (endoplasmic reticulum-derived) microsomal fraction. This indirect evidence that suggests ATP is required for phosphatidylserine translocation to the mitochondria is further supported by data obtained using permeabilized cells. Cells that have been permeabilized with saponin fail to decarboxylate newly synthesized phosphatidylserine unless they are supplemented with ATP. In contrast to the results obtained with intact and permeabilized cells are those obtained with isolated organelles which demonstrate that the final steps of phosphatidylserine import into the mitochondria occur in an ATP-independent manner. The current hypothesis is that phosphatidylserine translocation to the mitochondria occurs in at least two steps. The first step requires ATP and may be a process of vesicle budding or mechanical movement of an organelle such as the endoplasmic reticulum. The second step is ATP independent and most likely requires the formation of collision complexes between the donor organelle and the mitochondrion.