Mitochondrial fission in endothelial cells after simulated ischemia/reperfusion: Role of nitric oxide and reactive oxygen species

Randy J. Giedt, Changjun Yang, Jay L. Zweier, Anastasios Matzavinos, B. Rita Alevriadou

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Ischemia (I)/reperfusion (RP)-induced endothelial cell (EC) injury is thought to be due to mitochondrial reactive oxygen species (mtROS) production. MtROS have been implicated in mitochondrial fission. We determined whether cultured EC exposure to simulated I/RP causes morphological changes in the mitochondrial network and the mechanisms behind those changes. Because shear stress results in nitric oxide (NO)-mediated endothelial mtROS generation, we simulated I/RP as hypoxia (H) followed by oxygenated flow over the ECs (shear stress of 10 dyn/cm 2). By exposing ECs to shear stress, H, H/reoxygenation (RO), or simulated I/RP and employing MitoTracker staining, we assessed the differential effects of changes in mechanical forces and/or O 2 levels on the mitochondrial network. Static or sheared ECs maintained their mitochondrial network. H- or H/RO-exposed ECs underwent changes, but mitochondrial fission was significantly less compared to that in ECs exposed to I/RP. I/RP-induced fission was partially inhibited by antioxidants, a NO synthase inhibitor, or an inhibitor of the fission protein dynamin-related protein 1 (Drp1) and was accompanied by Drp1 oligomerization and phosphorylation (Ser616). Hence, shear-induced NO, ROS (including mtROS), and Drp1 activation are responsible for mitochondrial fission in I/RP-exposed ECs, and excessive fission may be an underlying cause of EC dysfunction in postischemic hearts.

Original languageEnglish (US)
Pages (from-to)348-356
Number of pages9
JournalFree Radical Biology and Medicine
Issue number2
StatePublished - Jan 15 2012
Externally publishedYes


  • Dynamin-related protein 1
  • Endothelial cell
  • Free radicals
  • Hypoxia/reoxygenation
  • Ischemia/reperfusion
  • Mitochondrial fission
  • Mitochondrial superoxide
  • Nitric oxide
  • Shear stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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