Thinking Mitochondrially


By Aysenur Gunaydin posted 03-20-2019 10:02



As a PhD candidate working on drug-induced mitochondrial toxicity at Istanbul University, it was incredible to see a Continuing Education course concerning “Structural and Functional Alterations of Mitochondria in Chemically Induced Cytotoxicity” in the SOT 58th Annual Meeting and ToxExpo Program. I immediately decided to sign up; I just couldn’t miss this course! Thanks to Bezmialem Vakif University supporting me with a congress grant, I was able to attend the Annual Meeting without difficulty. After I attended the course, I was particularly pleased to see that there is ongoing research by scientists all over the world focusing on mitochondrial toxicity, which made me feel a familiarity with the speakers and reminded me how important mitochondria are. I even had the chance to meet Dr. John J. Lemasters and ask him a question I had had for a while about some results of my experiments.

The course was very comprehensive. The first speaker, Dr. Mathieu Vinken, talked about adverse outcome pathways, focusing on ecotoxicology, general (cyto)toxicology, the central nervous system, and the liver in aspects of mitochondria. For example, the damage on the mitochondrial protein complex I eventually leads to parkinsonian inhibition. Mechanistic studies like this must increase to be able to predict the adverse outcomes of chemicals.

The second speaker, Dr. Hartmut Jaeschke (one of the chairs of the course), talked about “Mitochondria as Critical Regulators of Drug-Induced Organ Toxicity and Recovery” and how mitophagy limits acetaminophen-induced hepatotoxicity. He explained three mitochondrial biomarkers of APAP toxicity as cellular mechanistic biomarkers.

The third presentation, by Dr. John J. Lemasters, “Assessment of Mitochondrial Dysfunction in Drug- and Oxidant-Induced Cytotoxicity,” was very informative. He presented images of cells and presented the proton circuits of the mitochondria as analogous to electrical circuits.

The last presentation was given by the Chair of the course, Dr. Hilmi Orhan. He explained the local bioactivation of drugs in the mitochondria, which was highly interesting for me because I hadnt considered the role of the biotransformation enzymes of mitochondria before.

Thinking of mitochondrial changes in the cell as a key event in adverse outcome pathways or as critical regulators of drug-induced organ toxicity and recovery opens the door to the critical role of mitochondrial toxicity. It is well known that mitochondrial toxicity can be a mechanistic cause of drug toxicities, but unfortunately, it is not well focused in the preclinical step of testing. The mentality of mitochondrial biomarkers and improvement of the cooperation with computational toxicology can pave the way toward testing the chemicals in aspects of mitochondrial toxicity before marketing in the drug industry.

This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.