Its own architect: Flipping cardiolipin synthase.

Sci Adv

Department of Biochemistry and Molecular Biology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Published: January 2025

AI Article Synopsis

  • Current understanding posits that lipid asymmetry in cell membranes is actively kept and not essential for survival, yet the inner membrane (IM) shows notable asymmetry.
  • Researchers created a specific mutant lacking phosphatidylethanolamine (PE) that relies on cardiolipin (CL) for its IM viability, uncovering how the distribution of CL is regulated in the membrane.
  • The study reveals that the enzyme ClsA adapts its structure in response to varying levels of PE, highlighting a potentially novel mechanism for sustaining lipid asymmetry in membranes without the need for specialized flippase proteins.

Article Abstract

Current dogma assumes that lipid asymmetry in biological membranes is actively maintained and dispensable for cell viability. The inner (cytoplasmic) membrane (IM) of is asymmetric. However, the molecular mechanism that maintains this uneven distribution is unknown. We engineered a conditionally lethal phosphatidylethanolamine (PE)-deficient mutant in which the presence of cardiolipin (CL) on the periplasmic leaflet of the IM is essential for viability, revealing a mechanism that provides CL on the desired leaflet of the IM. CL synthase (ClsA) flips its catalytic cytoplasmic domain upon depletion of PE to supply nonbilayer-prone CL in the periplasmic leaflet of the IM for cell viability. In the presence of a physiological amount of PE, osmotic down-shock induces a topological inversion of ClsA, establishing the biological relevance of membrane protein reorientations in wild-type cells. These findings support a flippase-less mechanism for maintaining membrane lipid asymmetry in biogenic membranes by self-organization of a lipid-synthesizing enzyme.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698083PMC
http://dx.doi.org/10.1126/sciadv.ads0244DOI Listing

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