Document Type
Article
Publication Date
7-1-2018
Abstract
Objective: To explore the impact of oxidative insults on mitochondrial dynamics. In mammalian cells, oxidative insults activate stress response pathways including inflammation, cytokine secretion, and apoptosis. Intriguingly, mitochondria are emerging as a sensitive network that may function as an early indicator of subsequent cellular stress responses. Mitochondria form a dynamic network, balancing fusion, mediated by optic atrophy-1 (OPA1), and fission events, mediated by dynamin-related protein-1 (DRP1), to maintain homeostasis.
Methods: Here, we examine the impact of oxidative insults on mitochondrial dynamics in 143B osteosarcoma and H9c2 cardiomyoblast cell lines via confocal microscopy, flow cytometry, and protein-based analyses.
Results: When challenged with hydrogen peroxide (H2O2), a ROS donor, both cell lines display fragmentation of the mitochondrial network and loss of fusion-active OPA1 isoforms, indicating that OPA1-mediated mitochondrial fusion is disrupted by oxidative damage in mammalian cells. Consistent with this, cells lacking OMA1, a key protease responsible for cleavage of OPA1, are protected against OPA1 cleavage and mitochondrial fragmentation in response to H2O2 challenge.
Discussion: Taken together, these findings indicate that oxidative insults damage OPA1-mediated mitochondrial dynamics in mammalian cells via activation of OMA1, consistent with an emerging role for mitochondrial dynamics as an early indicator of cellular stress signaling.
Recommended Citation
Garcia, Iraselia, Wendy Innis-Whitehouse, Alma Lopez, Megan Keniry, and Robert Gilkerson. "Oxidative insults disrupt OPA1-mediated mitochondrial dynamics in cultured mammalian cells." Redox Report 23, no. 1 (2018): 160-167. http://doi.org/10.1080/13510002.2018.1492766
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
Redox Report
DOI
10.1080/13510002.2018.1492766
Comments
© 2018 The Author(s).