Holzerova 2015 Abstract MiP2015

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Impairment of reactive oxygen species defense system affects oxidative phosphorylation and causes early-onset neurodegeneration.


Holzerova E, Danhauser K, Haack TB, Kremer LS, Ingold I, Kobayashi S, Terrile C, Wolf P, Schaper J, Mayatepek E, Baertling F, Friedmann Angeli JP, Conrad M, Strom TM, Meitinger T, Prokisch H, Distelmaier F (2015)

Event: MiP2015

The umbrella term reactive oxygen species (ROS) comprises a wide array of partially reduced forms of oxygen, which are common by-products of cellular metabolism. Most intracellular ROS are derived from mitochondrial superoxide, which results from the monoelectronic reduction of oxygen. Superoxide is efficiently dismutated to hydrogen peroxide via superoxide dismutase, consequently making the mitochondria a major site for H2O2 generation. In this context, tight regulation of mitochondrial H2O2 levels is critical for their ability to participate in physiological cell signaling and to avoid nonspecific oxidative damage. Therefore, an efficient enzymatic machinery to buffer H2O2 levels has developed within the mitochondrial matrix. Key proteins involved in these processes are members of the thioredoxin (TXN) and the glutathione (GSH) systems.

In this study, we describe a 16-year-old adolescent suffering from early-onset neurodegeneration and severe cerebellar atrophy associated with a homozygous stop mutation in TXN2. This mutation increases reactive oxygen species levels, impaires oxidative stress defense and leads to secondary mitochondrial dysfunction with reduced cellular respiration and diminished ATP production. Animal studies suggest that TXN2 is essential during embryonic development. Supplementations with antioxidants effectively suppressed cellular ROS production, and lead to moderate clinical improvement during short term follow-up of the patient.

Labels: MiParea: nDNA;cell genetics, mt-Medicine, Patients  Pathology: Neurodegenerative  Stress:Oxidative stress;RONS 

Event: A1, Oral  MiP2015 


1-Inst Human Genetics, Tech Univ MΓΌnchen, Germany; 2-Inst Human Genetics, Helmholtz Zentrum MΓΌnchen, Neuherberg, Germany; 3-Dept Gen Ped, Neonatology Ped Card, Univ Children’s Hospital, DΓΌsseldorf, Germany; 4-Inst Dev Gen, Helmholtz Zentrum MΓΌnchen, Neuherberg, Germany; 5-Div Anim Prod, Spec Bioprod Science, Iwate Univ, Morioka, Iwate, Japan; 6-Med Fac, Dept of Diagnostic and Interventional Radiology, Univ DΓΌsseldorf, Germany. - [email protected]

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