Mitoch fission trggers ROS production

This paper tells about autophagy ( degradation of nerve cells) but also how mitochondrion fission activates it. I have earlier posted how too much iron will activate fission of mitochondria and hamper energy production in the mitochondria. PBT434 will most likely do just the opposite: it keeps the cells alive by improving energy supply and it promotes mitochondrial fusion and so prevents ROS production.

Biosci Biotechnol Biochem. 2018 Nov 26:1-8. doi: 10.1080/09168451.2018.1549933. [Epub ahead of print]
Drp1-dependent mitochondrial fission regulates p62-mediated autophagy in LPS-induced activated microglial cells.

Chae U¹, Kim HS¹, Lee HS¹, Lee SR², Lee DS¹.
Author information

1​

a School of Life Sciences and Biotechnology , BK21 Plus KNU Creative BioResearch Group, Kyungpook National University , Daegu , Republic of Korea.

2​

b National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Cheongju , Republic of Korea.
Abstract

Microglial activation is known to be an important event during innate immunity, but microglial inflammation is also thought to play a role in the etiology of neurodegenerative diseases. Recently, it was reported that autophagy could influence inflammation and activation of microglia. However, little is known about the regulation of autophagy during microglial activation. In this study, we demonstrated that mitochondrial fission-induced ROS can promote autophagy in microglia. Following LPS-induced autophagy, GFP-LC3 puncta were increased, and this was suppressed by inhibiting mitochondrial fission and mitochondrial ROS. Interestingly, inhibition of mitochondrial fission and mitochondrial ROS also resulted in decreased p62 expression, but Beclin1 and LC3B were unaffected. Taken together, these results indicate that ROS induction due to increased LPS-stimulated mitochondrial fission triggers p62 mediated autophagy in microglial cells. Our findings provide the first important clues towards understanding the correlation between mitochondrial ROS and autophagy. Abbreviations: Drp1; Dynamin related protein 1, LPS; Lipopolysaccharide, ROS; Reactive Oxygen Species, GFP; Green Fluorescent Protein, CNS; Central Nervous System, AD; Alzheimer's Disease, PD; Parkinson's Disease, ALIS; Aggresome-like induced structures, iNOS; inducible nitric oxide synthase, Cox-2; Cyclooxygenase-2, MAPK; Mitogen-activated protein kinase; SODs; Superoxide dismutase, GPXs; Glutathione Peroxidase, Prxs; Peroxiredoxins.​