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The outer membrane of Gram-negative bacteria is asymmetric, with phospholipids in the inner leaflet and lipopolysaccharides in the outer leaflet. Although the lipid asymmetry (Mla) pathway
has been implicated in trafficking phospholipids between the inner and outer membranes via retrograde transport, the directionality and mechanism of phospholipid transport was not well
understood. The pathway is composed of the outer membrane MlaA–OmpC–OmpF complex, a soluble periplasmic protein, MlaC, and the inner membrane ATPase, MlaFEDB complex. Knowles and colleagues
now provide evidence that the inner-membrane MlaFEDB complex, in particular the MlaD component, extracts phospholipids from the inner membrane and transfers them to MlaC in a manner
independent of ATP. The data suggest that the Mla pathway may be involved in anterograde phospholipid transport to the outer membrane.
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