Extracellular reactive oxygen species are generated by a plasma membrane oxidative phosphorylation system

Hyun Lee, Bong Woo Kim, Jung Woo Lee, Jin Hong, Jung Wha Lee, Hong Lim Kim, Jae Seon Lee, Young Gyu Ko

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Although the oxidative phosphorylation (OXPHOS) system has been found in mitochondria and the plasma membrane of various mammalian cell lines, understanding the physiological functions of the plasma membrane OXPHOS system is challenging. Here, we demonstrated that OXPHOS I, II, III, IV and V subunits were expressed in the plasma membrane of HepG2 cells and primary mouse hepatocytes, as determined by non-permeabilized immunofluorescence, total internal reflection fluorescence (TIRF) microscopy, cell surface-biotin labeling and plasma membrane and lipid raft isolation. Next, we demonstrated that NADH administration generated extracellular superoxide and improved insulin signaling in HepG2 cells and primary mouse hepatocytes. The NADH-dependent generation of extracellular superoxide was prevented by knockdown of NDUFV-1, the first subunit of OXPHOS I receiving electrons from NADH and the NADH-improved insulin signaling was abolished by extracellular catalase. Thus, we conclude that the OXPHOS system in the plasma membrane may be required for the generation of extracellular ROS and the regulation of insulin signaling.

Original languageEnglish
Pages (from-to)504-514
Number of pages11
JournalFree Radical Biology and Medicine
Publication statusPublished - 2017 Nov

Bibliographical note

Funding Information:
This work was supported by grants awarded to Y.-G. Ko from the Korea Health Industry Development Institute ( HI14C2739 ) and the National Research Foundation ( 2015R1A5A1009024 ). This was also partially supported by a Korea University grant (to Y.-G. Ko).

Publisher Copyright:
© 2017


  • Detergent-resistant lipid rafts
  • Extracellular superoxide
  • Insulin signaling
  • NADH
  • Plasma membrane oxidative phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


Dive into the research topics of 'Extracellular reactive oxygen species are generated by a plasma membrane oxidative phosphorylation system'. Together they form a unique fingerprint.

Cite this