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Cytochrome c Release from Dynamic Mitochondria in Endothelial Cells under Flow
Author(s) -
Hu YingLi,
Hur Sung Sik,
Chien Shu
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb647
Subject(s) - mitochondrion , laminar flow , cytochrome c , biophysics , cytochrome , chemistry , apoptosis , mitochondrial fission , microbiology and biotechnology , biology , biochemistry , physics , enzyme , thermodynamics
Endothelial mitochondria are essential to the functional integrity of endothelial cells (ECs) as they integrate a wide range of cellular processes. Cytochrome c (Cyt c) is located in the mitochondrial inner membrane space (IMS), where it functions in the electron transport chain. The morphology of mitochondria changes dynamically due to their frequent fusion and fission in response to cellular conditions. Mitochondrial fission is an early event during apoptosis and it occurs very close in time to Cyt c release, and fragmented mitochondria can readily be seen retaining Cyt c. ECs were subjected to oscillatory and laminar flows, with shear stresses of 0.4±4 and 12 dynes/cm 2 , respectively. Cyt c staining of the mitochondria was detected in ECs under both types of flow. In comparison to static control, Cyt c was significantly reduced in the mitochondria of ECs exposed to both flow patterns for 4 h, 8 h, and 24 h. The reduction of Cyt c in endothelial mitochondria was greater under oscillatory flow for 8 h and 24 h.4 h 8 h 24 hOscillatory Flow/Static 0.16±0.05 0.25±0.06 * 0.59±0.05 * Laminar Flow/Static 0.19±0.03 0.44±0.03 0.90±0.03Values are mean±SEM. * P<0.05 for Oscillatory vs. Laminar Flow.After laminar flow for 24 h, Cyt c rose to almost the level of the static ECs. We used time‐lapse imaging to monitor the spatial‐temporal dynamics of mitochondria in live ECs transfected with RFP‐mito. During live ECs shearing process mitochondria networks are dramatically reorganized from long filamentous, interconnected tubules into small punctate spheres in ECs under both flow patterns. Under oscillatory flow, more small fragmentations of endothelial mitochondria were observed than those under laminar flow. The results suggest that mechanical force affects the mitochondria dynamics in ECs under flow to cause Cyt c release, which was greater under oscillatory than laminar flow. Understanding of the endothelial mitochondria responses to different flow patterns will help to elucidate the mechanism of the region‐specific localization of atherosclerosis in the arterial system. Support or Funding Information This work was supported by NHLBI Research Grants HL‐104402 and HL‐106579 (S.C.)