TAILIEUCHUNG - Báo cáo khoa học: Accumulation of mitochondrial DNA damage and bioenergetic dysfunction in CSB defective cells

Cockayne syndrome (CS) is a complex, progressive disease that involves neurological and developmental impairment and premature aging. The majority of CS patients have mutations in theCSBgene. The CSB protein is involved in multiple DNA repair pathways and CSBmutated cells are sensitive to a broad spectrum of genotoxic agents. | Accumulation of mitochondrial DNA damage and bioenergetic dysfunction in CSB defective cells Pia 0. Osenbroch1 2 Pia Auk-Emblem1 2 Ruth Halsne1 2 Janne Strand1 2 Rune J. Forstr0m1 2 Ingrid van der Pluijm3 and Lars Eide1 2 1 Institute of ClinicalBiochemistry Faculty division Rikshospitalet University of Oslo Norway 2 Centre of Molecular Biology and Neuroscience Oslo Norway 3 DNage BV Department of Genetics Erasmus MedicalCenter Rotterdam The Netherlands Keywords ATP depletion CSB mtDNA damage oxidative stress supercomplex Correspondence L. Eide Institute of ClinicalBiochemistry Rikshospitalet University of Oslo Sognsvannsveien 20 0027 Oslo Norway Fax 47 2307 0902 Tel 47 2307 1062 E-mail Received 22 April2008 revised 11 February 2009 accepted 12 March 2009 doi Cockayne syndrome CS is a complex progressive disease that involves neurological and developmental impairment and premature aging. The majority of CS patients have mutations in the CSB gene. The CSB protein is involved in multiple DNA repair pathways and CSB mutated cells are sensitive to a broad spectrum of genotoxic agents. We tested the hypothesis that sensitivity to such genotoxins could be mediated by mitochondrial dysfunction as a consequence of the CSB mutation. mtDNA from csbm m mice accumulates oxidative damage including 8-oxoguanine and cells from this mouse are hypersensitive to the mitochondrial oxidant menadione. Inhibitors of mitochondrial complexes and the glycolysis inhibitor 2-deoxyglucose kill csbm m cells more efficiently than wild-type cells via a mechanism that does not correlate with mtDNA damage formation. Menadione depletes cellular ATP and recovery after depletion is slower in csbm m cells. The bioenergetic alteration in csbm m cells parallels the simpler organization of supercomplexes consisting of complexes I III and IV in addition to partially disassembled complex V in the inner mitochondrial membrane. Exposing wild-type cells

• Báo cáo khoa học
• Scientific reports
• scientific research
• biochemistry
• genetics
• Structural biochemistry
• Structural Biology
• collection of scientific reports
• industry reports philosophy of history reports
• reports in literature
• a scientific b shirt
• presentation of scientific reports
• reports on literature
• philosophy statement
• documents
• studies English language and English language communication and English language commercial
• progress reports at scientific collections
• agronomic reports
• reports in physics
• biology reports
• thematic biological
• induced geometry
• mathematical topics
• quantum mechanics
• physics
• reporting mathematics
• physics reports
• livestock reports
• physical reports
• research physicist
• specializing in physics
• mathematical statements
• mathematical equations
• English pronunciation
• presentation report
• agricultural reports
• technical crops
• bio technology
• English reports
• presentation reports
• mathematical knowledge
• reports of mathematics
• represented
• Wilf on packing distinct
• Tur´n density
• mathematical works
• patterns in a permutation
• statements and documents scientific reports
• reports agronomy
• biotechnology
• plants Vietnam
• specialized biological
• microbiological methods
• presenting the report
• anti bacterial properties of shrimp
• energy exchange
• engineering chicken
• Path counting
• random matrix theory
• Even circuits
• prescribed clockwise parity
• Correspondence between
• algorithmic characterizations
• Finding Induced Acyclic
• Random Digraphs
• Nonexistence results
• Hadamard like matrices
• Voltage Graphs
• Group Presentations
• Cages mathematical knowledge
• Dominance Order
• Graphical Partitions
• On the functions
• values in [α(G
• Box With Translates
• Two Given Rectangular Brick
• On the q analogue
• the sum of cubes