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

Keishi Suga, Akari Hamasaki, Junpei Chinzaka, Hiroshi Umakoshi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8-14
Number of pages7
JournalMetabolic Engineering Communications
Volume3
DOIs
Publication statusPublished - 2016 Dec 1
Externally publishedYes

Keywords

  • Cardiolipin
  • Isocitrate dehydrogenase
  • Liposome
  • Membranome
  • System biology

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biomedical Engineering

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