Translocation of phosphatidylthreonine and -serine to mitochondria diminishes exponentially with increasing molecular hydrophobicity.
Some cultured cells contain significant amounts of a rarely recognized phospholipid, phosphatidylthreonine. Since phosphatidylthreonine is a structural analog of phosphatidylserine, the question rises whether it is transported to mitochondria and decarboxylated to phosphatidylisopropanolamine therein. We studied this issue with hamster kidney cell-line using a novel approach, i.e. electrospray mass-spectrometry and stable isotope-labeled precursors. Scanning for a neutral loss of 155, which is characteristic for phosphatidylisopropanolamine, indicated that this lipid is indeed present. The identity of phosphatidylisopropanolamine was supported by the following: (i) it co-chromatographed with phosphatidylethanolamine; (ii) its molecular species profile was similar to that of phosphatidylethanolamine; (iii) its head group was labeled from 13C-threonine; and (iv) its concentration increased in parallel with phosphatidylthreonine. Tests with solubilized decarboxylase and subcellular fractionation studies indicated that the low cellular content of phosphatidylisopropanolamine is due to inefficient decarboxylation, rather than poor translocation of phosphatidylthreonine to mitochondria. Importantly, the average hydrophobicity of phosphatidylisopropanolamine molecular species was significantly less than that of phosphatidylthreonine species, indicating that hydrophilic phosphatidylthreonine species translocate to mitochondria far more rapidly than hydrophobic ones. Parallel results were obtained for phosphatidylserine. These findings imply that efflux from the ER membrane could be the rate-limiting step in the phosphatidylthreonine and -serine translocation to mitochondria.
Heikinheimo
Liisa
L
Institute of Biomedicine, Department of Biochemistry, University of Helsinki, Finland.
Somerharju
Pentti
P
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D006224:Cricetinae; D020404:Glycerophospholipids / Q000378:metabolism*; D008823:Micelles; D008928:Mitochondria / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013912:Threonine / Q000031:analogs & derivatives* / Q000378:metabolism*
D020404:Glycerophospholipids; D008823:Micelles; D010718:Phosphatidylserines; C017629:phosphatidylthreonine; D013912:Threonine