title: Loss of protein association causes cardiolipin degradation in Barth syndrome.
abstract: Cardiolipin is a specific mitochondrial phospholipid that has a high affinity for proteins and that stabilizes the assembly of supercomplexes involved in oxidative phosphorylation. We found that sequestration of cardiolipin in protein complexes is critical to protect it from degradation. The turnover of cardiolipin is slower by almost an order of magnitude than the turnover of other phospholipids. However, in subjects with Barth syndrome, cardiolipin is rapidly degraded via the intermediate monolyso-cardiolipin. Treatments that induce supercomplex assembly decrease the turnover of cardiolipin and the concentration of monolyso-cardiolipin, whereas dissociation of supercomplexes has the opposite effect. Our data suggest that cardiolipin is uniquely protected from normal lipid turnover by its association with proteins, but this association is compromised in subjects with Barth syndrome, leading cardiolipin to become unstable, which in turn causes the accumulation of monolyso-cardiolipin.
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, New York, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, New York University School of Medicine, New York, New York, USA.
authors.forename: Colin K L
authors.initials: CK
authors.lastname: Phoon
authors.affiliation: Department of Chemistry, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Bob
authors.initials: B
authors.lastname: Berno
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kenneth
authors.initials: K
authors.lastname: D'Souza
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York, USA.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.
authors.forename: Esthelle
authors.initials: E
authors.lastname: Hoedt
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York, USA.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.
authors.forename: Guoan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York, USA.|Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.
authors.forename: Thomas A
authors.identifier: 0000-0001-7049-2088
authors.initials: TA
authors.lastname: Neubert
authors.affiliation: Department of Chemistry, McMaster University, Hamilton, Ontario, Canada.|Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Epand
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, New York, USA.|Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
authors.forename: Mindong
authors.initials: M
authors.lastname: Ren
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, New York, USA.|Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlame
mesh_terms: D056889:Barth Syndrome / Q000378:metabolism*; D002308:Cardiolipins / Q000378:metabolism*; D006801:Humans
chemical_list: D002308:Cardiolipins