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Phosphatidylserine translocation into brain mitochondria: Involvement of a fusogenic protein associated with mitochondrial membranes

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Abstract

Data reported in the literature indicate that lipid movement between intracellular organelles can occur through contacts and close physical association of membranes (Vance, J.E. 1990. J Biol Chem 265: 7248-7256). The advantage of this mechanism is that the direct interaction of membranes provides the translocation event without the involvement of lipid-transport systems. However, pre-requisite for the functioning of this machinery is the presence of protein factors controlling membrane association and fusion. In the present work we have found that liposomes fuse to mitochondria at acidic pH and that the pre-treatment of mitochondria with pronase inhibits the fusogenic activity. Mixing of 14C-phosphatilyserine (PS) labeled liposomes with mitochondria at pH 6.0 results in the translocation of 14C-PS into mitochondria and in its decarboxylation to14 C-phosphatidylethanolamine through the PS decarboxylase activity localized on the outer surface of the inner mitochondrial membrane. Incorporation of 14C-PS is inhibited by the pre-treatment of mitochondria with pronase or with EEDQ, a reagent for the derivatization of the protonated form of carboxylic groups. These results indicate the presence of a protein associated with mitochondria which is able to trigger the fusion of liposomes to the mitochondrial membrane. A partial purification of a mitochondrial fusogenic glycoprotein is described in this work. The activity of the fusogenic protein appears to be dependent on the extent of protonation of the residual carboxylic groups and is influenced by the glucidic moiety, as demonstrated by its interaction with Concanavalin A. The purifed protein is able to promote the recover of the14 C-PS import from liposomes to pronase-treated mitochondria. Therefore, the protein is candidate to be an essential component in the machinery for the mitochondrial import of PS. (Mol Cell Biochem 175: 71–80, 1997)

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Camici, O., Corazzi, L. Phosphatidylserine translocation into brain mitochondria: Involvement of a fusogenic protein associated with mitochondrial membranes. Mol Cell Biochem 175, 71–80 (1997). https://doi.org/10.1023/A:1006889328983

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