Our group studies sheep pulmonary hypertension model for years and has shown increased mitochondrial ROS in pulmonary artery endothelial cells. At the same time the ER stress markers all increased. In some preliminary studies when we improved mitochondrial function then ER stress markers decreased. This happens in our animal model.    

Thank you Dr. Teng. This is interesting, and encouraging.

Although perhaps not directly what you are looking for, there is a connection between mitochondrial dysfunction and ROS production from the ER membrane in baker's yeast. See PMID: 23931758. 

Loss of cytochrome c oxidase promotes RAS-dependent ROS production from the ER resident NADPH oxidase, Yno1p, in yeast.

Leadsham JE, Sanders G, Giannaki S, Bastow EL, Hutton R, Naeimi WR, Breitenbach M, Gourlay CW.

Cell Metab. 2013 Aug 6;18(2):279-86. doi: 10.1016/j.cmet.2013.07.005.

Dr. Teng, you stated

"At the same time the ER stress markers all increased. In some preliminary studies when we improved mitochondrial function then ER stress markers decreased." May I ask which stress markers you were using?

I copy my answer as in our private communication below

"In acute stress I saw BiP/GRP78 surge while more prolonged change will be phosphorylated PERK/IRE1a, spliced XBP-1 (increased molecular weight) or cleaved ATF6 (decreased molecular weight). CHOP or Caspase12 in rodents are also increase. I like the review from CM Oslowski and F Urano in Method Enzymol 2011. Hope this can help you."

Thank you Dr. Causton

Hi Matthew,

Any role for mitochondrial ROS? Oxidative stress and ROS generation are integral components of ER stress and are NOT just consequences of ER stress induction. The major enzymatic components of ROS production during UPR induction are protein disulfide isomerase, endoplasmic reticulum oxidoreductin, and NADPH oxidase complexes, namely Nox4. Just additionally, mitochondrial electron transport enzymes produce ROS. So, the above role of the latter is close to zero in mammalian cells (not, say, in yeast). Although there are studies on ER stress and associated diseases, the core pathophysiological mechanism of ER stress-associated ROS has not yet been fully clarified.

Best wishes,

Ilya

 Thank you Dr. Tsyrlov.

Our study is in disease mechanisms of inflammatory myopathies (IIM). My interest in mitochondrial ROS is based on indications that up regulation of MHC1 is mediating ER stress, causing muscle damage.  We are hoping reduction of mitochondrial ROS and alleviation of mitochondria disfunction will help lower the ER stress and reduce muscle damage.  Any further comment?