Title: Mitochondrial fusion, fission, and biogenesis in prolonged critically ill patients
Authors: Vanhorebeek, Ilse ×
Gunst, Jan
Derde, Sarah
Derese, Inge
Boussemaere, Magaly
D'Hoore, André
Wouters, Pieter
Van den Berghe, Greet #
Issue Date: Jan-2012
Publisher: Issued for the Endocrine Society by the Williams & Wilkins Co.
Series Title: Journal of Clinical Endocrinology & Metabolism vol:97 issue:1 pages:E59-E64
Abstract: Context:Critical illness induces swelling, enlargement, and dysfunction of mitochondria, which in liver, but not in muscle, is aggravated by excessive hyperglycemia. We previously demonstrated impaired autophagic clearance of damaged mitochondria in fed prolonged critically ill patients. Impaired fusion/fission-mediated repair and/or renewal through biogenesis may further accentuate mitochondrial abnormalities.Objective:We studied mitochondrial fusion/fission and biogenesis and how these are affected by preventing hyperglycemia with insulin during critical illness.Design and Setting:Patients admitted to a university hospital surgical/medical intensive-care unit participated in a randomized study.Patients:We studied adult prolonged critically ill patients vs. controls.Intervention:Tolerating hyperglycemia up to 215 mg/dl was compared with intensive insulin therapy targeting normoglycemia (80-110 mg/dl).Main Outcome Measures:In liver and skeletal muscle, we quantified levels of several proteins involved in mitochondrial fusion/fission and biogenesis.Results:Key players in mitochondrial fusion/fission and biogenesis were up-regulated in postmortem liver (1.4- to 3.7-fold) and rectus abdominis (1.2- to 4.2-fold) but not in in vivo or postmortem vastus lateralis biopsies of critically ill patients. Maintaining normoglycemia with insulin attenuated the hepatic response in the mitochondrial fusion/fission process but did not affect the markers of mitochondrial biogenesis in liver or muscle.Conclusions:Our observations suggest tissue-dependent attempts of compensatory activation of mitochondrial repair mechanisms during critical illness. Considering the previously observed persistent mitochondrial damage, this activation may be insufficient and contribute to mitochondrial dysfunction. Suppressed activation of fusion/fission when excessive hyperglycemia is prevented with insulin may reflect reduced need for diluting (less) damage during normoglycemia or, alternatively, a suppressive effect of insulin on repair.
ISSN: 0021-972X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Intensive Care Medicine
Laboratory for Intensive Care Medicine (-)
Abdominal Surgical Oncology
Unit for Clinical-Translational Research (-)
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
OA_JCEM_jan_2012_Vanhorebeek.pdf Published 819KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science