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
2017
Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially
Luo X, Rosenfeld J, Yamamoto S, Harel T, Zuo Z, Hall M, Wierenga K, Pastore M, Bartholomew D, Delgado M, Rotenberg J, Lewis R, Emrick L, Bacino C, Eldomery M, Coban Akdemir Z, Xia F, Yang Y, Lalani S, Lotze T, Lupski J, Lee B, Bellen H, Wangler M, . Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially. PLOS Genetics 2017, 13: e1006905. PMID: 28742085, PMCID: PMC5557584, DOI: 10.1371/journal.pgen.1006905.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAnimals, Genetically ModifiedCalcium ChannelsCerebellar AtaxiaChildChild, PreschoolDrosophila melanogasterFemaleGenome, HumanGenome-Wide Association StudyHumansMaleMicroscopy, Electron, TransmissionMutation, MissenseNeurodegenerative DiseasesNeuroimagingPhenotypePoint MutationConceptsNeurodegenerative phenotypeGenomic rescue constructsS4 transmembrane segmentRescue constructTransmembrane segmentsFunction phenotypesLoss of functionMissense allelesFunction allelesWild typeGlobal developmental delayToxic gainMutant clonesDominant mutationsDevelopmental delayPoint mutationsDrosophilaFunctional impactPhenotypeQ-type voltage-dependent Ca2Early-onset developmental delayNeurological phenotypeAllelesSynaptic functionNovel variants