Liposomes modified with cardiolipin can act as a platform to regulate the potential flux of NADP+-dependent isocitrate dehydrogenase

Autor: Keishi Suga, Hiroshi Umakoshi, Junpei Chinzaka, Akari Hamasaki
Jazyk: angličtina
Rok vydání: 2015
Předmět:
0301 basic medicine
CL
cardiolipin
System biology
lcsh:Biotechnology
Endocrinology
Diabetes and Metabolism
Biomedical Engineering
Phospholipid
TCA
tricarboxylic acid
Biology
Ch
cholesterol
NADPH
β-nicotinamide-adenine dinucleotide phosphate reduced form
Article
NADP+
β-nicotinamide-adenine dinucleotide phosphate oxidized form
03 medical and health sciences
chemistry.chemical_compound
ld
liquid-disordered
lcsh:TP248.13-248.65
so
solid-ordered
Membranome
Cardiolipin
Inner mitochondrial membrane
Lipid bilayer
PDB
protein data bank
lcsh:QH301-705.5
Liposome
ICDH
isocitrate dehydrogenase
030102 biochemistry & molecular biology
DPPC
1
2-dipalmitoyl-sn-glycero-3-phosphocholine
LUV
large unilamellar vesicles
Isocitrate dehydrogenase
Cytosol
030104 developmental biology
Membrane
lcsh:Biology (General)
chemistry
Biochemistry
MLV
multilamellar vesicles
lipids (amino acids
peptides
and proteins)
OMM
outer mitochondrial membrane
lo
liquid-ordered
IMM
inner mitochondrial membrane
Zdroj: Metabolic Engineering Communications
Metabolic Engineering Communications, Vol 3, Iss, Pp 8-14 (2016)
ISSN: 2214-0301
Popis: Cardiolipin (CL) is a phospholipid found in the outer mitochondrial membrane (OMM) and inner mitochondrial membrane (IMM) in animal cells. Isocitrate dehydrogenase (ICDH) is an important catalytic enzyme that is localized at the cytosol and mitochondria; the metabolic pathway catalyzed by ICDH differs between the OMM and IMM. To estimate the possible role of lipid membrane in the enzymatic activity of NADP+-dependent ICDH, CL-modified liposomes were prepared using CL/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/cholesterol (Ch), and their characteristics were analyzed based on the fluorescent probe method. The relative enzymatic activity of ICDH decreased in the presence of CL/DPPC/Ch=(30/50/20) liposome, whereas activity increased in the presence of CL/DPPC/Ch=(5/75/20) liposome. NADP+ had the greatest substrate affinity and was dominant in the regulation of ICDH activity. Analysis of membrane properties indicated that membranes in CL-modified liposomes were dehydrated by ICDH binding. Using circular dichroism analysis, CL/DPPC/Ch=(30/50/20) liposome induced a conformational change in ICDH, indicating that CL-rich membrane domains could inhibit ICDH activity. These results suggest that lipid membranes, including CL molecules, could act as a platform to regulate ICDH-related metabolic pathways such as the tricarboxylic acid cycle and lipid synthesis.
Graphical abstract
Highlights • Phosphatidylcholine liposomes were modified with cardiolipin and characterized. • DPPC liposomes did not affect the activity of ICDH. • ICDH activity was enhanced with liposomes at 5 mol% cardiolipin. • ICDH activity was lowered with liposomes at 30 mol% cardiolipin. • Liposomes with high content of cardiolipin led to conformational changes of ICDH.
Databáze: OpenAIRE
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