DLP1‐dependent mitochondrial fragmentation mediates heat shock‐induced injury in mouse C2C12 skeletal muscle cells
Abstract
Mitochondria regulate cell survival and coordinate cell‐wide stress responses by constantly changing their shapes to alterations in energy demands and/or environmental stimuli. In this study, we investigated the role of mitochondrial morphology in heat‐induced injury in mouse C2C12 skeletal muscle cells. Exposure to heat for 4 hours significantly reduced cell viability (96 ± 3 % at 37 °C vs. 62 ± 6 % at 43 °C, p < 0.01). Mitochondrial morphology analysis revealed that heat exposure caused rapid mitochondrial fragmentation (cells contained fragmented mitochondria: 9 ± 1 %, 47 ± 4 % and 91 ± 2 % at 0, 15 and 30 min, respectively). To identify the molecular mechanism(s) underlying heat‐induced mitochondrial fragmentation, we performed immunoblotting and immunostaining for mitochondrial fission and fusion proteins. Heat exposure increased mitochondrial translocation of fission factor dynamin‐like protein 1 (DLP1). Furthermore, loss of mitochondrial membrane potential and subsequent cleavage of mitochondrial fusion protein optic atrophy 1 (OPA1) in C2C12 cells were noted following heat exposure. Pretreatment with DLP1 chemical inhibitor Mdivi‐1 or knockdown of DLP1 gene expression reduced mitochondrial fragmentation, prevented loss of mitochondrial membrane potential, and improved viability of C2C12 cells in response to heat shock. These results suggest that heat stress is associated with altered mitochondrial dynamics and DLP1‐mediated mitochondrial fission serves a role in heat‐induced cell injury.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2016
- Source ID
- 10.1096/fasebj.30.1_supplement.747.1
Entities
People
- Patricia A. Deuster
- Tianzheng Yu
- Yifan Chen
Organizations
- Congressionally Directed Medical Research Programs
- Uniformed Services University of the Health Sciences