ArticleScientific reports2017
A missense MT-ND5 mutation in differentiated Parkinson Disease cytoplasmic hybrid induces ROS-dependent DNA Damage Response amplified by DROSHA.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 28 citations in OpenAlex.
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- Abnormal lipid droplets accumulation induced cognitive deficits in obstructive sleep apnea syndrome mice via JNK/SREBP/ACC pathway but not through PDP1/PDC pathway.Molecular medicine (Cambridge, Mass.) · 2022Article
- High-Resolution Imaging of Mitochondria and Mitochondrial Nucleoids in Differentiated SH-SY5Y Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- MicroRNA‑93 knockdown inhibits acute myeloid leukemia cell growth via inactivating the PI3K/AKT pathway by upregulating DAB2.International journal of oncology · 2021Article
- p38 MAPK-mediated loss of nuclear RNase III enzyme Drosha underlies amyloid beta-induced neuronal stress in Alzheimer's disease.Aging cell · 2021Article
- Assessment of the impact of mitochondrial genotype upon drug-induced mitochondrial dysfunction in platelets derived from healthy volunteers.Archives of toxicology · 2021Article
- DROSHA is recruited to DNA damage sites by the MRN complex to promote non-homologous end joining.Journal of cell science · 2021Article
- Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson's Disease via Activating the JAK2/STAT3 Pathway.Frontiers in neuroscience · 2021Article
- The Role of Mitonuclear Incompatibility in Bipolar Disorder Susceptibility and Resilience Against Environmental Stressors.Frontiers in genetics · 2021Review
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- Heat Shock Affects Mitotic Segregation of Human Chromosomes Bound to Stress-Induced Satellite III RNAs.International journal of molecular sciences · 2020Article
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- Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis.Oxidative medicine and cellular longevity · 2019Review
- The Krebs Cycle Connection: Reciprocal Influence Between Alternative Splicing Programs and Cell Metabolism.Frontiers in oncology · 2018Review
- Integrative Analysis of Mitochondrial-Related Genes Reveals Diagnostic Biomarkers and Therapeutic Targets in Acute Pancreatitis.IET systems biologyArticle
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome integrity is continuously threatened by endogenous sources of DNA damage including reactive oxygen species (ROS) produced by cell metabolism. Factors of the RNA interference (RNAi) machinery have been recently involved in the cellular response to DNA damage (DDR) in proliferating cells. To investigate the impact of component of RNAi machinery on DDR activation in terminally differentiated cells, we exploited cytoplasmic hybrid (cybrid) cell lines in which mitochondria of sporadic Parkinson's disease patients repopulate neuroblastoma SH-SY5Y-Rho(0) cells. Upon differentiation into dopaminergic neuron-like cells, PD63 cybrid showed increased intracellular level of ROS and chronic DDR activation, compared to other cybrids with the same nuclear background. Importantly, DDR activation in these cells can be prevented by ROS scavenging treatment suggesting that ROS production is indeed causative of nuclear DNA damage. Sequence analysis of the mitogenomes identified a rare and heteroplasmic missense mutation affecting a highly conserved residue of the ND5-subunit of respiratory complex I, which accounts for ROS increase. We demonstrated that the assembly of nuclear DDR foci elicited by oxidative stress in these cells relies on DROSHA, providing the first evidence that components of RNAi machinery play a crucial role also in the mounting of ROS-induced DDR in non-replicating neuronal cells.
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