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Temelie 2018 Oxid Med Cell Longev
Additional label Labels  + , 2018-07  +
Coupling states OXPHOS  + , ET  +
Diseases Aging;senescence  + , Cancer  +
Has abstract Impaired mitochondrial function and accumu
Impaired mitochondrial function and accumulation of DNA damage have been recognized as hallmarks of age-related diseases. Mitochondrial dysfunction initiates protective signalling mechanisms coordinated at nuclear level particularly by modulating transcription of stress signalling factors. In turn, cellular response to DNA lesions comprises a series of interconnected complex protective pathways, which require the energetic and metabolic support of the mitochondria. These are involved in intracellular as well as in extracellular signalling of damage. Here, we have initiated a study that addresses how mitochondria-nucleus communication may occur in conditions of combined mitochondrial dysfunction and genotoxic stress and what are the consequences of this interaction on the cell system. In this work, we used cells deficient for PINK1, a mitochondrial kinase involved in mitochondrial quality control whose loss of function leads to the accumulation of dysfunctional mitochondria, challenged with inducers of DNA damage, namely, ionizing radiation and the radiomimetic bleomycin. Combined stress at the level of mitochondria and the nucleus impairs both mitochondrial and nuclear functions. Our findings revealed exacerbated sensibility to genotoxic stress in PINK1-deficient cells. The same cells showed an impaired induction of bystander phenomena following stress insults. However, these cells responded adaptively when a challenge dose was applied subsequently to a low-dose treatment to the cells. The data demonstrates that PINK1 modulates intracellular and intercellular signalling pathways, particularly adaptive responses and transmission of bystander signalling, two facets of the cell-protective mechanisms against detrimental agents.
ive mechanisms against detrimental agents.  +
Has editor [[Kandolf G]]  +
Has info [ Open Access]  +
Has title Temelie M, Savu DI, Moisoi N (2018) Intracellular and intercellular signalling mechanisms following DNA damage are modulated by PINK1. Oxid Med Cell Longev 1391387.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  + , Mouse  +
MiP area Respiration  + , nDNA;cell genetics  + , Genetic knockout;overexpression  +
Pathways N  + , NS  +
Preparation Permeabilized cells  +
Tissue and cell Nervous system  + , Other cell lines  + , Fibroblast  +
Was published by MiPNetLab UK Leicester Moisoi N +
Was published in journal Oxid Med Cell Longev +
Was published in year 2018  +
Was written by Temelie M + , Savu DI + , Moisoi N +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
11:55:24, 24 July 2018  +
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