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Forward or backward, that is the question: phospholipid trafficking by the Mla system

Lookup NU author(s): Dr Javier Abellon-RuizORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022 The Author(s).The distinctive feature of Gram-negative bacteria is the presence of an asymmetric outer membrane (OM), which acts as a permeation barrier blocking the diffusion of noxious components such as antibiotics that could compromise cell survival. The outer membrane has an inner leaflet, mainly formed by phospholipids (PLs), and the outer leaflet, composed of molecules of lipopolysaccharide (LPS). Building this membrane is a very complex process as every OM element needs to be transported from the cytoplasm or the inner membrane and properly placed in the OM. In addition, the asymmetry needs to be maintained to guarantee the barrier function of the membrane. The presence of misplaced PLs in the outer leaflet of the OM causes increased permeability, endangering cell survival. The Mla system (maintenance of OM lipid asymmetry) has been linked to the removal of the misplaced PLs, restoring OM asymmetry. The Mla system has elements in all compartments of the cell envelope: the lipoprotein MlaA in complex with the trimeric porins OmpC/F in the OM, MlaC in the periplasmic space and an ABC transporter in the inner membrane called MlaFEDB. While genetic and structural work suggest that the Mla pathway is retrograde (PL movement from OM to IM), several groups have advocated that transport could happen in an anterograde fashion (from IM to OM). However, recent biochemical studies strongly support retrograde transport. This review provides an overview of the current knowledge of the Mla system from a structural point of view and addresses the latest biochemical findings and their impact in transport directionality.

Publication metadata

Author(s): Abellon-Ruiz J

Publication type: Article

Publication status: Published

Journal: Emerging Topics in Life Sciences

Year: 2023

Volume: 7

Issue: 1

Pages: 125-135

Print publication date: 01/03/2023

Online publication date: 02/12/2022

Acceptance date: 14/11/2022

Date deposited: 27/04/2023

ISSN (print): 2397-8554

ISSN (electronic): 2397-8562

Publisher: Portland Press Ltd.


DOI: 10.1042/ETLS20220087

PubMed id: 36459067


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Funder referenceFunder name
214222/Z/18/ZWellcome Trust