title: Increasing mitochondrial membrane phospholipid content lowers the enzymatic activity of electron transport complexes.
abstract: Activities of the enzymes involved in cellular respiration are markedly influenced by the composition of the phospholipid environment of the inner mitochondrial membrane. Contrary to previous suppositions, we show that fusion of mitochondria isolated from healthy cardiac muscle with cardiolipin or dioleoylphosphatidylcholine results in a 2-6-fold reduction in the activity of complexes I, II, and IV. The activity of complex III was unaffected by increased phospholipid levels. Phospholipid content had an indiscriminate yet detrimental effect on the combined activities of complexes I+III and II+III. These results have strong implications for therapeutic lipid replacement strategies, in which phospholipid modification of the mitochondria is proposed to enhance mitochondrial function.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University , Greenville, North Carolina 27834, United States.
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.forename: E Madison
authors.initials: EM
authors.lastname: Sullivan
authors.forename: Rick J
authors.initials: RJ
authors.lastname: Alleman
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Tonya N
authors.initials: TN
authors.lastname: Zeczycki
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000378:metabolism; D019069:Cell Respiration / Q000502:physiology; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats
chemical_list: D002308:Cardiolipins; D045222:Electron Transport Chain Complex Proteins; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D009243:NAD; C017251:1,2-oleoylphosphatidylcholine