Plasmalogens and Photooxidative Stress Signaling in Myxobacteria, and How it Unmasked CarF/TMEM189 as the Δ1′-Desaturase PEDS1 for Human Plasmalogen Biosynthesis

Abstract

Plasmalogens are glycerophospholipids with a hallmark sn-1 vinyl ether bond that endows them with unique physical-chemical properties. They have proposed biological roles in membrane organization, fluidity, signaling, and antioxidative functions, and abnormal plasmalogen levels correlate with various human pathologies, including cancer and Alzheimer’s disease. The presence of plasmalogens in animals and in anaerobic bacteria, but not in plants and fungi, is well-documented. However, their occurrence in the obligately aerobic myxobacteria, exceptional among aerobic bacteria, is often overlooked. Tellingly, discovery of the key desaturase indispensable for vinyl ether bond formation, and therefore fundamental in plasmalogen biogenesis, emerged from delving into how the soil myxobacterium Myxococcus xanthus responds to light. A recent pioneering study unmasked myxobacterial CarF and its human ortholog TMEM189 as the long-sought plasmanylethanolamine desaturase (PEDS1), thus opening a crucial door to study plasmalogen biogenesis, functions, and roles in disease. The findings demonstrated the broad evolutionary sweep of the enzyme and also firmly established a specific signaling role for plasmalogens in a photooxidative stress response. Here, we will recount our take on this fascinating story and its implications, and review the current state of knowledge on plasmalogens, their biosynthesis and functions in the aerobic myxobacteria.

Lipidomic Analysis Reveals Differences in Bacteroides Species Driven Largely by Plasmalogens, Glycerophosphoinositols and Certain Sphingolipids

“…Plasmalogens, or vinyl ether lipids, are produced by the modification of the fatty acid at the sn-1 position of GP such that it is linked via an alkenyl or plasmenyl bond rather than an ester bond ( Figure 3 shows the structure of PE Plasmalogen). Plasmalogens have a broad phylogenetic distribution; they are present in biological membranes of bacteria, protozoa, invertebrates and mammals [ 41 ]. Amongst bacteria, plasmalogens are rarely detected in aerobes [ 42 ]; they are sparse in facultative anaerobes [ 43 ] but appear to be common in anaerobes including certain gut-associated Bifidobacteria and Clostridia species [ 43 , 44 , 45 , 46 , 47 , 48 ].…”

Membrane lipids from gut microbiome-associated bacteria as structural and signalling molecules

“…Plasmalogens have a broad phylogenetic distribution, being found in many biological membranes from bacteria, protozoa, invertebrates and mammals. Amongst bacteria, with the exception of myxobacteria [42], plasmalogens are not found in aerobes and are rarely found in facultative anaerobes, but appear to be common in anaerobes, including certain gut-associated Bifidobacteria, Clostridia and Bacteroides [34,[43][44][45][46][47][48][49]. In mammals, plasmalogen biosynthesis involves the oxygen-dependent conversion of an ester to a vinyl ether [50,51].…”

Plasmalogens and platelet‐activating factor roles in chronic inflammatory diseases

“…[38][39][40][41] Recently, the gene encoding plasmenylethanolamine desaturase in humans was further identified as the transmembrane protein (TMEM189), which introduces the characteristic vinyl ether double bond into Pls. 42,43 Pls degradation might occur either via non-enzymatic or enzymatic reactions. 44 The nonenzymatic mechanisms of Pls degradation are chemical in nature and depend on vinyl-ether bond oxidation or hydrolysis; that is oxygen radical or acid attack removing the alkyl chain at sn-1 position of the glycerol moiety.…”

“…Fatty acyl‐CoA reductase 1 (Far1) is an enzyme bound to the peroxisomal surface membrane, which has been proposed to constitute a rate‐limiting reaction for Pls biosynthesis 38–41 . Recently, the gene encoding plasmenylethanolamine desaturase in humans was further identified as the transmembrane protein (TMEM189), which introduces the characteristic vinyl ether double bond into Pls 42,43 . Pls degradation might occur either via non‐enzymatic or enzymatic reactions 44 .…”