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1. Exogenous Fatty Acids Remodel Staphylococcus aureus Lipid Composition through Fatty Acid Kinase

   https://doi.org/10.1128/JB.00128-20  

   DeMars, Zachary; Singh, Vineet K.; Bose, Jeffrey L. (June 2020, Journal of Bacteriology)

   Stock, Ann M. (Ed.)

   ABSTRACT Staphylococcus aureus can utilize exogenous fatty acids for phospholipid synthesis. The fatty acid kinase FakA is essential for this utilization by phosphorylating exogenous fatty acids for incorporation into lipids. How FakA impacts the lipid membrane composition is unknown. In this study, we used mass spectrometry to determine the membrane lipid composition and properties of S. aureus in the absence of fakA . We found the fakA mutant to have increased abundance of lipids containing longer acyl chains. Since S. aureus does not synthesize unsaturated fatty acids, we utilized oleic acid (18:1) to track exogenous fatty acid incorporation into lipids. We observed a concentration-dependent incorporation of exogenous fatty acids into the membrane that required FakA. We also tested how FakA and exogenous fatty acids impact membrane-related physiology and identified changes in membrane potential, cellular respiration, and membrane fluidity. To mimic the host environment, we characterized the lipid composition of wild-type and fakA mutant bacteria grown in mouse skin homogenate. We show that wild-type S. aureus can incorporate exogenous unsaturated fatty acids from host tissue, highlighting the importance of FakA in the presence of host skin tissue. In conclusion, FakA is important for maintaining the composition and properties of the phospholipid membrane in the presence of exogenous fatty acids, impacting overall cell physiology. IMPORTANCE Environmental fatty acids can be harvested to supplement endogenous fatty acid synthesis to produce membranes and circumvent fatty acid biosynthesis inhibitors. However, how the inability to use these fatty acids impacts lipids is unclear. Our results reveal lipid composition changes in response to fatty acid addition and when S. aureus is unable to activate fatty acids through FakA. We identify concentration-dependent utilization of oleic acid that, when combined with previous work, provides evidence that fatty acids can serve as a signal to S. aureus . Furthermore, using mouse skin homogenates as a surrogate for in vivo conditions, we showed that S. aureus can incorporate host fatty acids. This study highlights how exogenous fatty acids impact bacterial membrane composition and function. 

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2. Electrophysiological Characterization of Monoolein-Fatty Acid Bilayers

   https://doi.org/10.1021/acs.langmuir.4c03814  

   Scott, Caroline; Porteus, Riley; Takeuchi, Shoji; Osaki, Toshihisa; Lee, Sunghee (January 2025, Langmuir)
3. Modulating fatty acid metabolism and composition of CHO cells by feeding high levels of fatty acids complexed using methyl-β-cyclodextrin

   https://doi.org/10.1016/j.ymben.2025.04.005  

   Priem, Bradley; Cai, Xiangchen; Hong, Yu-Jun; Gilmore, Karl; Deng, Zijun; Chen, Sabrina; Naik, Harnish Mukesh; Betenbaugh, Michael J; Antoniewicz, Maciek R (September 2025, Metabolic Engineering)
4. SREBP activation contributes to fatty acid accumulations in necroptosis

   https://doi.org/10.1039/d2cb00172a  

   Lu, Daniel; Parisi, Laura R.; Gokcumen, Omer; Atilla-Gokcumen, G. Ekin (April 2023, RSC Chemical Biology)

   Necroptosis is a type of programmed cell death. It is characterized by membrane permeabilization and is associated with the release of intracellular components due to compromised membrane integrity which induces a strong inflammatory response. We recently showed that the accumulation of very long chain fatty acids (VLCFAs) contributes to membrane permeabilization during necroptosis. However, the mechanisms that result in the accumulation of these cytotoxic lipids remain unknown. Using comparative transcriptomics and digital PCR validations, we found that several target genes of sterol regulatory element-binding proteins (SREBPs) were upregulated during necroptosis, suggesting that they might be responsible for the accumulation of VLCFA in this process. We demonstrated that activation of SREBPs during necroptosis exacerbates the permeability of the plasma membrane and cell death. Consistent with these observations, targeting sterol regulatory element-binding protein cleavage-activating protein (SCAP), a protein involved in SREBP activation, reversed the accumulation of VLCFAs, and restored cell death and membrane permeabilization during necroptosis. Collectively, our results highlight a role for SREBP in regulating lipid changes during necroptosis and suggest SREBP-mediated lipid remodeling as a potential target for therapeutics to reduce membrane permeabilization during necroptosis. 

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5. Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration

   https://doi.org/10.3390/nu12113523  

   Sarparast, Morteza; Dattmore, Devon; Alan, Jamie; Lee, Kin Sing (November 2020, Nutrients)

   null (Ed.)

   Due to the aging population in the world, neurodegenerative diseases have become a serious public health issue that greatly impacts patients’ quality of life and adds a huge economic burden. Even after decades of research, there is no effective curative treatment for neurodegenerative diseases. Polyunsaturated fatty acids (PUFAs) have become an emerging dietary medical intervention for health maintenance and treatment of diseases, including neurodegenerative diseases. Recent research demonstrated that the oxidized metabolites, particularly the cytochrome P450 (CYP) metabolites, of PUFAs are beneficial to several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease; however, their mechanism(s) remains unclear. The endogenous levels of CYP metabolites are greatly affected by our diet, endogenous synthesis, and the downstream metabolism. While the activity of omega-3 (ω-3) CYP PUFA metabolites and omega-6 (ω-6) CYP PUFA metabolites largely overlap, the ω-3 CYP PUFA metabolites are more active in general. In this review, we will briefly summarize recent findings regarding the biosynthesis and metabolism of CYP PUFA metabolites. We will also discuss the potential mechanism(s) of CYP PUFA metabolites in neurodegeneration, which will ultimately improve our understanding of how PUFAs affect neurodegeneration and may identify potential drug targets for neurodegenerative diseases. 

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