title: The physical state of lipid substrates provides transacylation specificity for tafazzin.
abstract: Cardiolipin is a mitochondrial phospholipid with a characteristic acyl chain composition that depends on the function of tafazzin, a phospholipid-lysophospholipid transacylase, although the enzyme itself lacks acyl specificity. We incubated isolated tafazzin with various mixtures of phospholipids and lysophospholipids, characterized the lipid phase by (31)P-NMR and measured newly formed molecular species by MS. Substantial transacylation was observed only in nonbilayer lipid aggregates, and the substrate specificity was highly sensitive to the lipid phase. In particular, tetralinoleoyl-cardiolipin, a prototype molecular species, formed only under conditions that favor the inverted hexagonal phase. In isolated mitochondria, <1% of lipids participated in transacylations, suggesting that the action of tafazzin was limited to privileged lipid domains. We propose that tafazzin reacts with non-bilayer-type lipid domains that occur in curved or hemifused membrane zones and that acyl specificity is driven by the packing properties of these domains.
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, NY, USA. michael.schlame@med.nyu.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Schlame
authors.forename: Devrim
authors.initials: D
authors.lastname: Acehan
authors.forename: Bob
authors.initials: B
authors.lastname: Berno
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valvo
authors.forename: Mindong
authors.initials: M
authors.lastname: Ren
authors.forename: David L
authors.initials: DL
authors.lastname: Stokes
authors.forename: Richard M
authors.initials: RM
authors.lastname: Epand
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D008051:Lipid Bilayers; D050356:Lipid Metabolism; D008823:Micelles; D019906:Nuclear Magnetic Resonance, Biomolecular; D013379:Substrate Specificity
chemical_list: D029721:Drosophila Proteins; D008051:Lipid Bilayers; D008823:Micelles; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C514176:tafazzin protein, Drosophila