Hoel 2017 MiPschool Obergurgl
Event: MiPschool Obergurgl 2017
Impaired mitochondrial function may result in aberrant ROS production, insufficient supply of ATP, cellular damage and cell death. Optimal mitochondrial function is maintained by fission and fusion processes that shape the mitochondrial network and morphology, the elimination of dysfunctional mitochondrial through mitophagy and the generation of new mitochondria through biogenesis. These processes are crucial for adaptation during stress conditions, and have also been linked to diseases such as Parkinson’s disease.
In this study we have investigated the effects of different types of mitochondrial stressors on these adaptive processes by exposing cultured SH-SY5Y neuroblastoma cells to sub-lethal doses of different OXPHOS inhibitors (Rotenone, Oligomycin, Antimycin A, Myxothiazol) for 72 hours. Our focus was to investigate proteins that are involved in the dynamics, quality control and biogenesis of mitochondria.
We found that exposure to electron transport chain (ETC) inhibitors resulted in clear changes in expression of mitochondrial shaping proteins. These changes were accompanied by increases in the levels of PINK1 and p62, most apparent in the cells exposed to the complex III inhibitors Myxothiazol and Antimycin A. The finding that inhibition of different OXPHOS complexes caused different responses, suggests that the effects are not caused by reduced bioenergetics function alone depended on which OXPHOS, and are likely to involve ROS.
Our data suggest that mitochondrial stress responses due to defective OXPHOS depend on which complex that is affected. The effects on proteins involved in mitochondrial shaping and autophagy suggested that central parts of the mitochondrial quality control system were compromised, or possibly overcharged.
Labels: MiParea: Respiration, mtDNA;mt-genetics
Organism: Human Tissue;cell: Nervous system
Regulation: Inhibitor Coupling state: LEAK Pathway: ROX
Event: B1 MiPschool Obergurgl 2017
- Dept Biomedicine, Univ Bergen, Norway.- [email protected]