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Mitochondrial unfolded protein response (mtUPR) participates in hepatic dysfunction in sepsis
Author(s) -
Huang LiJu,
Ho JiaJing,
Yang ReiCheng
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.872.5
Subject(s) - sepsis , mitochondrion , unfolded protein response , proteostasis , microbiology and biotechnology , biology , homeostasis , organelle , chaperone (clinical) , bioenergetics , hsp60 , heat shock protein , immunology , hsp70 , medicine , gene , biochemistry , endoplasmic reticulum , pathology
Mitochondrial dysfunction‐induced bioenergetic failure seems to be a primary event in sepsis‐ensued multiple organ failure. Accumulation of ROS leads to a stressed situation and increase the pool of unfolded and misfolded proteins in mitochondria. The mitochondrial unfolded protein response (mtUPR) is one of the mitochondria‐nuclear communication, that activates transcription of nuclear‐encoded mitochondrial chaperone ( hsp60/10 ) genes to promote protein homeostasis within the organelle. Therefore, the mtUPR is the most important protein quality control system in oxidative stress‐ related pathology. From our previous studies in a cecal ligation and puncture (CLP) sepsis model, we have found that content of ATP decreased, membrane potential decreased, apoptosis increased, etc. Nevertheless, we also found most of the adverse effects could be reversed by previous overproduction of chaperone proteins. These results encourage us to further investigate whether disarrangement of the mtUPR may contribute to the result of a cell energetic failure that correlates with hepatic dysfunction in sepsis. The results are positive and showed that the response could be induced 3 hours after sepsis induction but then these chaperone proteins decreased along with the progress of sepsis. In conclusion, we suggested that mtUPR failure occurred during sepsis and the index of mtUPR may be a valuable additional measurement in assessing the risk of organ dysfunction in the clinical setting.