TY  - JOUR
A1  - Dröse, Stefan
A1  - Stepanova, Anna
A1  - Galkin, Alexander
T1  - Ischemic A/D transition of mitochondrial complex I and its role in ROS generation
T2  - Biochimica et Biophysica Acta. Bioenergetics
N2  - Mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a key enzyme in cellular energy metabolism and provides approximately 40% of the proton-motive force that is utilized during mitochondrial ATP production. The dysregulation of complex I function--either genetically, pharmacologically, or metabolically induced--has severe pathophysiological consequences that often involve an imbalance in the production of reactive oxygen species (ROS). Slow transition of the active (A) enzyme to the deactive, dormant (D) form takes place during ischemia in metabolically active organs such as the heart and brain. The reactivation of complex I occurs upon reoxygenation of ischemic tissue, a process that is usually accompanied by an increase in cellular ROS production. Complex I in the D-form serves as a protective mechanism preventing the oxidative burst upon reperfusion. Conversely, however, the D-form is more vulnerable to oxidative/nitrosative damage. Understanding the so-called active/deactive (A/D) transition may contribute to the development of new therapeutic interventions for conditions like stroke, cardiac infarction, and other ischemia-associated pathologies. In this review, we summarize current knowledge on the mechanism of A/D transition of mitochondrial complex I considering recently available structural data and site-specific labeling experiments. In addition, this review discusses in detail the impact of the A/D transition on ROS production by complex I and the S-nitrosation of a critical cysteine residue of subunit ND3 as a strategy to prevent oxidative damage and tissue damage during ischemia-reperfusion injury. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.
KW  - Mitochondrial complex I
KW  - Ischemia/reperfusion injury
KW  - ROS generation
KW  - A/D transition
KW  - Thiol redox modification
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/42381
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-423810
SN  - 0005-2728
N1  - © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
VL  - 1857
IS  - 7
SP  - 946
EP  - 957
PB  - Elsevier
CY  - Amsterdam
ER  -