Hu 2017 Proc Natl Acad Sci U S A

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Hu H, Nan J, Sun Y, Zhu D, Xiao C, Wang Y, Zhu L, Wu Y, Zhao J, Wu R, Chen J, Yu H, Hu X, Zhu W, Wang J (2017) Electron leak from NDUFA13 within mitochondrial complex I attenuates ischemia-reperfusion injury via dimerized STAT3. Proc Natl Acad Sci U S A 114:11908-13.

» PMID: 29078279 Open Access

Hu Hengxun, Nan Jinliang, Sun Yong, Zhu Dan, Xiao Changchen, Wang Yaping, Zhu Lianlian, Wu Yue, Zhao Jing, Wu Rongrong, Chen Jinghai, Yu Hong, Hu Xinyang, Zhu Wei, Wang Jian'an (2017) Proc Natl Acad Sci U S A

Abstract: The causative relationship between specific mitochondrial molecular structure and reactive oxygen species (ROS) generation has attracted much attention. NDUFA13 is a newly identified accessory subunit of mitochondria complex I with a unique molecular structure and a location that is very close to the subunits of complex I of low electrochemical potentials. It has been reported that down-regulated NDUFA13 rendered tumor cells more resistant to apoptosis. Thus, this molecule might provide an ideal opportunity for us to investigate the profile of ROS generation and its role in cell protection against apoptosis. In the present study, we generated cardiac-specific tamoxifen-inducible NDUFA13 knockout mice and demonstrated that cardiac-specific heterozygous knockout (cHet) mice exhibited normal cardiac morphology and function in the basal state but were more resistant to apoptosis when exposed to ischemia-reperfusion (I/R) injury. cHet mice showed a preserved capacity of oxygen consumption rate by complex I and II, which can match the oxygen consumption driven by electron donors of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD)+ascorbate. Interestingly, at basal state, cHet mice exhibited a higher H2O2 level in the cytosol, but not in the mitochondria. Importantly, increased H2O2 served as a second messenger and led to the STAT3 dimerization and, hence, activation of antiapoptotic signaling, which eventually significantly suppressed the superoxide burst and decreased the infarct size during the I/R process in cHet mice.

Keywords: NDUFA13, STAT3, Hydroxyl peroxide, Mitochondria, Reactive oxygen species Bioblast editor: Kandolf G O2k-Network Lab: CN Hangzhou Zhu W


Labels: MiParea: Respiration, Genetic knockout;overexpression 

Stress:Cell death, Ischemia-reperfusion, Oxidative stress;RONS  Organism: Mouse 

Preparation: Isolated mitochondria 

Regulation: Inhibitor  Coupling state: OXPHOS  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

Labels, 2017-12, CN