Wojtala 2014 Abstract MiP2014
|Proteomic analysis of mitochondrial Complex I deficient mouse model - impact of Complex I deficiency on p66Shc-Ser36 phosphorylation pathway in NDUFS4-/- mouse tissues.|
Key mitochondrial energy-providing reactions are carried out by the oxidative phosphorylation system (OXPHOS), involving the electron transfer and phosphorylation systems including F1Fo-ATP synthase. The most common OXPHOS disorder in humans is associated with Complex I deficiency, leading to fatal encephalomyopathies of early childhood- Leigh-like syndrome . The growth factor adaptor protein p66Shc has a substantial impact on mitochondrial metabolism through regulation of cellular responses to oxidative stress. A low level of p66Shc protein or its complete ablation protects against numerous age-related disorders and may partially prevent pathologies caused by reactive oxygen species (ROS). On the other hand, a high level of p66Shc phosphorylation is correlated with increased intracellular ROS production [2,3].
Organs from NDUFS4-/- mice with Complex I deficiency were used as a model of self-propelling intracellular oxidative stress. The status of the antioxidant defense system, oxidative stress markers and the p66Shc-Ser36 phosphorylation pathway were measured in these tissues. Mass spectrometry analysis was also performed for selected NDUFS4-/- mouse tissues.
In our study, mice with defective Complex I were characterized by attenuated intracellular oxidative stress, connected with increased p66Shc phosphorylation. Mass spectrometry revealed aberrations in the level of Complex I proteins and oxidative stress- related proteins, as well as other proteins involved in metabolic processes.
• O2k-Network Lab: NL Nijmegen Koopman WJ
Stress:Oxidative stress;RONS Organism: Mouse
Enzyme: Complex I
Event: A1, P-flash MiP2014
1-Dep Biochem, Nencki Inst Experimental Biol, Warsaw, Poland; 2-Radbound Univ Medical Centre, Nijmegen, The Netherlands. - firstname.lastname@example.org
References and acknowledgements
This work was supported by the Statutory Founding from Nencki Institute of Experimental Biology and Polish Ministry of Science and Higher Education grant W100/HFSC/2011.
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