title: Increasing levels of cardiolipin differentially influence packing of phospholipids found in the mitochondrial inner membrane.
abstract: It is essential to understand the role of cardiolipin (CL) in mitochondrial membrane organization given that changes in CL levels contribute to mitochondrial dysfunction in type II diabetes, ischemia-reperfusion injury, heart failure, breast cancer, and aging. Specifically, there are contradictory data on how CL influences the molecular packing of membrane phospholipids. Therefore, we determined how increasing levels of heart CL impacted molecular packing in large unilamellar vesicles, modeling heterogeneous lipid mixtures found within the mitochondrial inner membrane, using merocyanine (MC540) fluorescence. We broadly categorized lipid vesicles of equal mass as loosely packed, intermediate, and highly packed based on peak MC540 fluorescence intensity. CL had opposite effects on loosely versus highly packed vesicles. Exposure of loosely packed vesicles to increasing levels of CL dose-dependently increased membrane packing. In contrast, increasing amounts of CL in highly packed vesicles decreased the packing in a dose-dependent manner. In vesicles that were categorized as intermediate packing, CL had either no effect or decreased packing at select doses in a dose-independent manner. Altogether, the results aid in resolving some of the discrepant data by demonstrating that CL displays differential effects on membrane packing depending on the composition of the lipid environment. This has implications for mitochondrial protein activity in response to changing CL levels in microdomains of varying composition.
authors.affiliation: Department of Biochemistry & Molecular Biology, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States; East Carolina Diabetes & Obesity Institute, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States.
authors.forename: Tonya N
authors.initials: TN
authors.lastname: Zeczycki
authors.affiliation: Department of Biochemistry & Molecular Biology, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States; East Carolina Diabetes & Obesity Institute, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States.
authors.forename: Jarrett
authors.initials: J
authors.lastname: Whelan
authors.affiliation: Department of Biochemistry & Molecular Biology, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States; East Carolina Diabetes & Obesity Institute, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States.
authors.forename: William Tyler
authors.initials: WT
authors.lastname: Hayden
authors.affiliation: East Carolina Diabetes & Obesity Institute, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States; Department of Physiology, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.affiliation: Department of Biochemistry & Molecular Biology, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States; East Carolina Diabetes & Obesity Institute, East Carolina Heart Institute Building, Brody School of Medicine, East Carolina University, 115 Heart Drive, Greenville, NC 27834, United States. Electronic address: shaiksa@ecu.edu.
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
mesh_terms: D032701:Biomimetics / Q000379:methods; D002308:Cardiolipins / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology*; D008563:Membrane Lipids / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D053835:Unilamellar Liposomes / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; D008563:Membrane Lipids; D010743:Phospholipids; D053835:Unilamellar Liposomes
keywords: Cardiolipin; Lipid vesicles; Membrane packing; Mitochondria