Survival in Critical Illness Is Associated with Early Activation of Mitochondrial Biogenesis
- 14 September 2010
- journal article
- research article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 182 (6), 745-751
- https://doi.org/10.1164/rccm.201003-0326OC
Abstract
Rationale: We previously reported outcome-associated decreases in muscle energetic status and mitochondrial dysfunction in septic patients with multiorgan failure. We postulate that survivors have a greater ability to maintain or recover normal mitochondrial functionality. Objectives: To determine whether mitochondrial biogenesis, the process promoting mitochondrial capacity, is affected in critically ill patients. Methods: Muscle biopsies were taken from 16 critically ill patients recently admitted to intensive care (average 1-2 d) and from 10 healthy, age-matched patients undergoing elective hip surgery. Measurements and Main Results: Survival, mitochondrial morphology, mitochondrial protein content and enzyme activity, mitochondrial biogenesis factor mRNA, microarray analysis, and phosphorylated (energy) metabolites were determined. Ten of 16 critically ill patients survived intensive care. Mitochondrial size increased with worsening outcome, suggestive of swelling. Respiratory protein subunits and transcripts were depleted in critically ill patients and to a greater extent in nonsurvivors. The mRNA content of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (transcriptional coactivator of mitochondrial biogenesis) was only elevated in survivors, as was the mitochondrial oxidative stress protein manganese superoxide dismutase. Eventual survivors demonstrated elevated muscle ATP and a decreased phosphocreatine/ATP ratio. Conclusions: Eventual survivors responded early to critical illness with mitochondrial biogenesis and antioxidant defense responses. These responses may partially counteract mitochondrial protein depletion, helping to maintain functionality and energetic status. Impaired responses, as suggested in nonsurvivors, could increase susceptibility to mitochondrial damage and cellular energetic failure or impede the ability to recover normal function.Keywords
This publication has 51 references indexed in Scilit:
- Exercise Stimulates Pgc-1α Transcription in Skeletal Muscle through Activation of the p38 MAPK PathwayPublished by Elsevier BV ,2005
- Mitochondria in health and disease: perspectives on a new mitochondrial biologyMolecular Aspects of Medicine, 2004
- Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1Cell, 1999
- Stimulation of liver RNA and protein breakdown in endotoxemic rats: role of glucocorticoids.1999
- Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care unitsCritical Care Medicine, 1998
- Persistent inhibition of cell respiration by nitric oxide: Crucial role ofS-nitrosylation of mitochondrial complex I and protective action of glutathioneProceedings of the National Academy of Sciences of the United States of America, 1998
- Adenine/Ribose Supply Increases Adenosine Production and Protects ATP Pool in Adenosine Kinase-inhibited Cardiac CellsJournal of Molecular and Cellular Cardiology, 1998
- A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive ThermogenesisCell, 1998
- Extramitochondrial ATP/ADP-Ratios Regulate Cytochrome c Oxidase Activity via Binding to the Cytosolic Domain of Subunit IVBiological Chemistry, 1998
- Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteinsAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1989