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.

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MiP2014, Book of Abstracts Open Access

Wojtala A, Koopman W, Willems PH, Smeitink JA, Duszynski J, Wieckowski MR (2014)

Event: MiP2014

Key mitochondrial energy-providing reactions are carried out by the oxidative phosphorylation system (OXPHOS), involving the electron transfer and phosphorylation systems including F₁F_o-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 [1]. 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.

Labels:

Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.  Organism: Mouse 

Enzyme: Complex I 

MiP2014 

Affiliation

1-Dep Biochem, Nencki Inst Experimental Biol, Warsaw, Poland; 2-Radbound Univ Medical Centre, Nijmegen, The Netherlands. - [email protected]

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.

1. Distelmaier F, Koopmann WJ, van den Heuvel PL, Rodenburg RJ, Mayatepek E, Willems PH, Smeitink JA (2009) Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. Brain 132: 833–42.
2. Pinton P, Rimessi A, Marchi S, Orsini F, Migliaccio E, Giorgio M, Contursi C, Minucci S, Mantovani F, Wieckowski MR, Del Sal G, Pelicci PG, Rizzuto R (2007) Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 315: 659-63.
3. Suski JM, Karkucinska-Wieckowska A, Lebiedzinska M, Giorgi C, Szczepanowska J, Szabadkai G, Duszynski J, Pronicki M, Pinton P, Wieckowski MR (2011) p66Shc aging protein in control of fibroblasts cell fate. Int J Mol Sci 12: 5373-89.