Dear Dr. Mohammad Shadab

Mitochondria are the source of many pro-inflammatory signals that cause the activation of the immune system and generate inflammatory responses.

Two key factors that determine the structural and functional integrity of mitochondria are mitochondrial ion channels and transporters. They are not only important for maintaining the ionic homeostasis of the cell, but also play a role in regulating reactive oxygen species generation, ATP production, calcium homeostasis and apoptosis, which are common pro-inflammatory signals. In addition, oxidized mtDNA is also involved in activating the inflammasome complex.

So, knowledge with respect to the ionic conductance in mitochondria upon severe inflammatory conditions is necessary to recognize their significance in maintaining ionic homeostasis. If one understands the role and mechanisms of mitochondrial ion channels in elucidating inflammatory response, it will help provide new targets for therapeutics, which can be utilized as a treatment for many severe inflammatory disorders.

You may want to refer to the review article attached below for more information.

https://www.frontiersin.org/articles/10.3389/fphys.2020.00258/full

Best.

Thank you Malcolm Nobre for such a nice answer. I agree that the components of mitochondria you highlighted are indeed involved in trigerring inflammation. The question I aksed is why mitochondria exhibit such response that I mean to say there are other orgenelles also in the cell but why is it unique to mitochondria?

Dr. Mohammad Shadab , free radicals and other reactive oxygen species (ROS) are frequently associated with being harmful. However, several physiological functions (differentiation, cellular signaling, phosphorylation/dephosphorylation events and apoptosis) are dependent on the presence of reactive species inside the cells. To regulate these cellular functions, the ROS production must be kept low. When it increases, ROS becomes dangerous, determining undesirable effects on cellular structures, including intracellular organelles, and participating in the onset and/or progression of several human disorders.

Yes, there are other organelles in the cell, for instance, ROS are generated in the peroxisomes compartment by oxidases and NO synthases that produce hydrogen peroxide (H2O2) and NO, respectively. Then we have the ER that represents a place where high amounts of ROS are produced. In this compartment, ROS result in being the byproduct of oxidases and oxygenase involved during the protein folding process, such as ER oxidoreductin1.

Moreover, ER present iron deposits that contribute to form the reactive species hydroxyl radical (·OH). But among all these, mitochondria represent the primary source of ROS (mitochondrial ROS, mtROS) for the cell. ROS are key signaling molecules that play an important role in the progression of inflammatory disorders. Today, many questions regarding the molecular function of mtROS and of mito-inflammation need to be investigated. I hope in the coming years these will be addressed so that researchers may be able to develop new mitochondria-targeted therapies.

You may be interested in the papers attached below.

Article Mitochondrial Oxidative Stress and “Mito-Inflammation”: Acto...

Article Reactive Oxygen Species in Inflammation and Tissue Injury

Article Role of Reactive Oxygen Species in Inflammation: A Minireview

Article Crosstalk between reactive oxygen species and pro-inflammato...

Best.