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Upregulation of mitophagy in enterocytes during intestinal ischemia in rats
Author(s) -
Kalogeris Theodore John,
Wang Meifang,
Korthuis Ronald J.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1209.10
Subject(s) - mitophagy , mitochondrion , ischemia , pink1 , cytosol , mfn2 , mitochondrial matrix , enterocyte , biology , chemistry , microbiology and biotechnology , medicine , endocrinology , mitochondrial fusion , apoptosis , small intestine , biochemistry , mitochondrial dna , autophagy , gene , enzyme
Intestinal ischemia reperfusion (I/R) elicits decreases in mitochondrial respiratory activity and membrane potential, as well as an increase in the mitochondrial‐dependent apoptotic pathway in intestinal enterocytes. However the precise roles of ischemia versus reperfusion in post‐ischemic mitochondrial dysfunction in the gut are unclear. In these studies we have begun to examine the kinetics of mitochondrial dysfunction during the ischemic period. Intestinal enterocytes were isolated from rats after graded periods (up to 40 min) of occlusion of the superior mesenteric artery, and mitochondrial membrane potential (Ψ) and markers of mitophagy and mitochondrial mass were measured. Mitochondrial Ψ (measured by TMRE fluorescence), showed a slight increase by 10 min, but was significantly decreased by 20–40 min ischemia. The autophagosome marker, LC3, showed a time‐dependent increase in the LC3‐II/LC3‐I ratio from 20–40 min ischemia, and there was a shift in the relative distribution of parkin from cytosol to mitochondria by 40 min. Ischemia also elicited cytosolic release of cytochrome c, and decreases in mitochondrial Mfn2 and porin by 40 min. These results indicate that post‐ischemic mitochondrial dysfunction in intestinal enterocytes is preceded by changes in mitochondrial function even prior to reperfusion. Supported by NIH AA‐014945 and HL‐095486.