Mfsd2a utilizes a flippase mechanism to mediate omega-3 fatty acid lysolipid transport
Abstract
Significance Mfsd2a is a transporter expressed at the blood–brain barrier that mediates the major pathway by which the brain acquires essential fatty acids from blood. Mfsd2a transports fatty acids conjugated as lysophosphatidylcholine (LPC) in blood circulation. Humans with loss of function mutations in Mfsd2a present with severe microcephaly, indicating a critical role of LPC transport in brain development. A model for Mfsd2a transport posits that Mfsd2a acts as a LPC “flippase,” inverting LPC as it moves through the transporter from the outer to inner leaflet of the plasma membrane. By establishing an in vitro biochemical assay, this study provides the direct proof that Mfsd2a has “flippase” activity, thus defining the biochemical mechanism of how LPC is transported into the brain.
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