Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Increased risk of sudden death in untreated Primary Carnitine Deficiency

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Newborn screening for homocystinurias: recent recommendations versus current practice

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences in the form of oxidative stress, has been linked to a wide variety of diseases including inborn errors of metabolism. In this review we will summarize how the functional state of mitochondria -- and especially the concentration of reactive oxygen species (ROS), produced in connection with the respiratory chain -- regulates cellular stress responses by redox regulation of nuclear gene networks involved in repair systems to maintain cellular homeostasis and health. Based on our own and other's studies we re-introduce the ROS triangle model and discuss how inborn errors of mitochondrial metabolism, by production of pathological amounts of ROS, may cause disturbed redox signalling and induce chronic cell stress with non-resolving or compromised cell repair responses and increased susceptibility to cell stress induced cell death. We suggest that this model may have important implications for those inborn errors of metabolism, where mitochondrial dysfunction plays a major role, as it allows the explanation of oxidative stress, metabolic reprogramming and altered signalling growth pathways that have been reported in many of the diseases. It is our hope that the model may facilitate novel ideas and directions that can be tested experimentally and used in the design of future new approaches for pre-symptomatic diagnosis and prognosis and perhaps more effective treatments of inborn errors of metabolism.

Original languageEnglish
JournalJournal of Inherited Metabolic Disease
Volume38
Issue number4
Pages (from-to)703-19
Number of pages17
ISSN0141-8955
DOIs
Publication statusPublished - Jul 2015

    Research areas

  • Humans, Metabolism, Inborn Errors, Mitochondrial Diseases, Organelle Biogenesis, Oxidation-Reduction, Oxidative Stress, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't, Review

ID: 49590351