Premium
Deficiency of Apoptosis Inducing Factor (AIF) decreases complex I activity and increases the ROS generation in isolated cardiac mitochondria
Author(s) -
Szczepanek Karol,
Hu Ying,
Lesnefsky Edward,
Chen Qun
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.1085.18
Subject(s) - mitochondrion , reactive oxygen species , oxidative phosphorylation , downregulation and upregulation , apoptosis , apoptosis inducing factor , rotenone , glutamate receptor , mitochondrial ros , oxidative stress , chemistry , biology , microbiology and biotechnology , medicine , endocrinology , biochemistry , programmed cell death , caspase , gene , receptor
Objective Genomic downregulation of mitochondrial AIF content in Harlequin (Hq) mice increases cardiac injury during ischemia‐reperfusion (IR). We investigated if the AIF deficiency in cardiac mitochondria affects the rate of oxidative phosphorylation (OXPHOS) and the electron transport chain (ETC)‐mediated generation of reactive oxygen species (ROS). Methods The rate of OXPHOS, complex I activity, and the net release of H 2 O 2 were determined in isolated mitochondria from Hq or wild type (WT) mouse hearts. Results Downregulation of AIF expression inhibited the rate of OXPHOS using glutamate and malate (Glu+mal) as complex I substrates (Table). The complex I activity was also decreased in Hq mouse heart mitochondria vs. WT. The net release of H 2 O 2 was increased in Hq mitochondria vs. WT, using both complex I and complex II substrates (Succinate + rotenone, Succ+ROT). Conclusion Mitochondrial AIF deficiency leads to a defect at the proximal portion of ETC and increased generation of ROS from the ETC. This setting likely contributes to increased cardiac injury in Hq mice during IR. This work was supported by the American Heart Association (QC, 11SDG5120011) and the Department of Veterans Affairs (EJL).