2023
A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels
Dutta D, Kanca O, Byeon S, Marcogliese P, Zuo Z, Shridharan R, Park J, Lin G, Ge M, Heimer G, Kohler J, Wheeler M, Kaipparettu B, Pandey A, Bellen H. A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels. Nature Metabolism 2023, 5: 1595-1614. PMID: 37653044, PMCID: PMC11151872, DOI: 10.1038/s42255-023-00873-0.Peer-Reviewed Original ResearchConceptsFatty acid synthesisFe-S cluster biogenesisMitochondrial fatty acid synthesisCeramide levelsMost eukaryotic cellsElevated ceramide levelsIron metabolismCluster biogenesisEukaryotic cellsLoss of functionCellular lipidomeEnoyl coenzymeNeurodegenerative phenotypeIron homeostasisHuman-derived fibroblastsMechanistic linkAcid synthesisCeramideMECRMetabolismNeurodegenerationMtFASBiogenesisLast stepMitochondria
2018
Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain
Lin G, Lee P, Chen K, Mao D, Tan K, Zuo Z, Lin W, Wang L, Bellen H. Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain. Cell Metabolism 2018, 28: 605-618.e6. PMID: 29909971, DOI: 10.1016/j.cmet.2018.05.019.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-SynucleinAnimalsBrainCell Line, TumorCeramidesDrosophilaDrosophila ProteinsFeedback, PhysiologicalFemaleGroup VI Phospholipases A2Group X Phospholipases A2HeLa CellsHumansLysosomesMaleMembrane FluidityMutationNeuronsNuclear ProteinsParkinson DiseaseRNA-Binding ProteinsSphingolipidsVesicular Transport ProteinsConceptsIPLA2-VIAImpairs synaptic transmissionEarly-onset parkinsonismSynaptic transmissionNeuroaxonal dystrophyParkinson's diseaseNeuronal functionBrain tissueNeurodegenerative disordersΑ-synucleinPLA2G6Ceramide levelsProgressive increaseNeurodegenerationLysosomal stressPositive feedback loopRetromer functionPhospholipid compositionCeramideGlycerol phospholipidsParkinsonismVPS35Desipramine