Unknown

Dataset Information

0

Oxidative insults disrupt OPA1-mediated mitochondrial dynamics in cultured mammalian cells.


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.

SUBMITTER: Garcia I 

PROVIDER: S-EPMC6272060 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Oxidative insults disrupt OPA1-mediated mitochondrial dynamics in cultured mammalian cells.

Garcia Iraselia I   Innis-Whitehouse Wendy W   Lopez Alma A   Keniry Megan M   Gilkerson Robert R  

Redox report : communications in free radical research 20181201 1


<h4>Objective</h4>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-relate  ...[more]

Similar Datasets

| S-EPMC4429534 | biostudies-literature
| S-EPMC7603527 | biostudies-literature
| S-EPMC3856479 | biostudies-literature
| S-EPMC3760005 | biostudies-literature
| S-EPMC4023816 | biostudies-other
| S-EPMC5015069 | biostudies-other
| S-EPMC3989652 | biostudies-literature
| S-EPMC524759 | biostudies-literature
| S-EPMC9866574 | biostudies-literature
| S-EPMC6282049 | biostudies-literature