A mitochondrial pathway for biosynthesis of lipid mediators : Nature Chemistry : Nature Publishing Group

The central role of mitochondria in metabolic pathways and in cell-death
mechanisms requires sophisticated signalling systems. Essential in this
signalling process is an array of lipid mediators derived from
polyunsaturated fatty acids. However, the molecular machinery for the
production of oxygenated polyunsaturated fatty acids is localized in the
cytosol and their biosynthesis has not been identified in mitochondria.
Here we report that a range of diversified polyunsaturated molecular
species derived from a mitochondria-specific phospholipid, cardiolipin
(CL), is oxidized by the intermembrane-space haemoprotein, cytochrome c.
We show that a number of oxygenated CL species undergo phospholipase A₂-catalysed
hydrolysis and thus generate multiple oxygenated fatty acids, including
well-known lipid mediators. This represents a new biosynthetic pathway
for lipid mediators. We demonstrate that this pathway, which includes
the oxidation of polyunsaturated CLs and accumulation of their
hydrolysis products (oxygenated linoleic, arachidonic acids and
monolysocardiolipins), is activated in vivo after acute tissue injury.