INTRACELLULAR TRAFFICKING OF PHOSPHOLIPIDS - IMPORT OF PHOSPHATIDYLSERINE INTO MITOCHONDRIA

Three mechanisms are commonly suggested for the movement of lipids bet ween intracellular organelles: transfer mediated by cytosolic lipid tr ansfer proteins, vesicle-mediated transfer, and transfer via regions o f membrane continuity between organelles. The mechanism of translocati on of phosphatidylserine from its site of synthesis on the endoplasmic reticulum (and related membranes) to the site of phosphatidylserine d ecarboxylation in the mitochondria has been investigated. Several expe riments indicate that a transfer mediated by soluble cytosolic phospho lipid transfer proteins, or by vesicles, is unlikely. Rather, the most likely mode of import of newly-synthesized phosphatidylserine into mi tochondria is contact between the endoplasmic reticulum and mitochondr ial membranes. In support of this mechanism we have isolated and endop lasmic reticulum-like ''mitochondria-associated membrane'' fraction an d shown that it has some, but not all, properties of the endoplasmic r eticulum. The mitochondria-associated membranes are enriched in lipid biosynthetic enzymes, especially phosphatidylserine synthase. When eit her phosphatidylserine translocation to mitochondria is blocked (by AT P depletion), or phosphatidylserine decarboxylation is blocked (with h ydroxylamine), newly-synthesized phosphatidylserine accumulates in the mitochondria-associated membrane but not in microsomes, suggesting th at phosphatidylserine traverses the mitochondria-associated membrane o n its route from the endoplasmic reticulum to mitochondria.