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Dr. Derek McKay

Event Start: Mar 14, 2018 1:00 pm
Location: School of Medicine, 132A

Dr. Derek McKay

Professor, Dept. Physiology & Pharmacology,
Canada Research Chair (Tier 1) in Intestinal Immunophysiology
University of Calgary

Mitochondria regulate epithelial-bacteria interactions: implications for the gut barrier

The microbiota of the gut is an important determinant of health and well-being, where loss of diversity is described in inflammatory bowel disease (IBD): bacteria can be found within the gut epithelium of patients with IBD, and their epithelial barrier function is often decreased.  Deranged epithelial mitochondria can also occur in enterocytes from patients with IBD.  I will present one mechanism by which targeted disruption of mitochondrial function with the uncoupling agent, dinitrophenol, results in increased internalization of non-invasive E. coli by metabolically-stressed epithelial.  Considering connectivity with the transporting epithelial cell, mitochondria are functionally coupled to the ER, and ER stress (an unfolded protein response) has been described in IBD.  I hypothesized that the combination of ER and mitochondrial stress would significantly disrupt epithelial barrier function. Contrary to my expectation, induction of ER-stress protects against decreased barrier function caused by disruption of mitochondrial function, as assessed by viable intracellular bacteria and E. coli transcytosis. ER-stress did not prevent DNP-driven uptake of bacteria; rather, specific mobilization of the ATF6-arm of ER stress and then DAPK-1 resulted in enhanced autophagic killing of bacteria.  Finally, epithelia infected with the putative pathobiont, adherent-invasive E. coli (AIEC, strain LF82) demonstrate significant fragmentation of their mitochondrial network.  Collectively, these studies are revealing the importance of mitochondrial function in regulating the host-microbe relationship, specifically enteric epithelial-commensal bacteria interaction, which may identify novel ways to maintain homeostasis and promote digestive health.

March 14th, 2018
1:00 - 2:00pm
School of Medicine, Room 132A