The fate of damaged mitochondrial DNA in the cell

Liao, Siyang; Chen, Li; Song, Zhiyin; He, He

doi:10.1016/j.bbamcr.2022.119233

Cited by 35 publications

(21 citation statements)

References 84 publications

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“…Previous reports demonstrated that mitochondrial damage leads to dysfunction and subsequently damages the nuclear components of the cell. 34…”

Section: Resultsmentioning

confidence: 99%

“…Previous reports demonstrated that mitochondrial damage leads to dysfunction and subsequently damages the nuclear components of the cell. 34 The significant effect of MMA on the nuclear condensation and disruption of nucleic acids was detected using the Hoechst 33258 staining assay. The dysfunction of mitochondria significantly destroys the nuclear components of the cells such as DNA and RNA and subsequently induces apoptosis.…”

Section: Morphological Changesmentioning

confidence: 99%

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LC-HRMS analysis of corn mint Mentha arvensis L. for anticancer activity against triple-negative breast cancer targeting inflammatory and apoptosis signaling pathways

Pratyusha,

Sparjan Samuvel,

Nivetha

et al. 2024

New J. Chem.

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“…Previous reports demonstrated that mitochondrial damage leads to dysfunction and subsequently damages the nuclear components of the cell. 34…”

Section: Resultsmentioning

confidence: 99%

Section: Morphological Changesmentioning

confidence: 99%

LC-HRMS analysis of corn mint Mentha arvensis L. for anticancer activity against triple-negative breast cancer targeting inflammatory and apoptosis signaling pathways

Pratyusha,

Sparjan Samuvel,

Nivetha

et al. 2024

New J. Chem.

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show abstract

“…DNA damage occurs routinely in the human body, resulting from various factors like UV radiation, X‐rays, γ‐rays, chemical agents, and reactive oxygen species (ROS) (Chatterjee & Walker, 2017; Jeggo et al., 2016; Liao et al., 2022; Norbury & Zhivotovsky, 2004; Schumacher et al., 2021). Accumulation of DNA damage can lead to senescence and cancer (Jeggo et al., 2016; Schumacher et al., 2021).…”

Section: Introductionmentioning

confidence: 99%

Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence

Huang,

Zhuang,

et al. 2024

J of Extracellular Vesicle

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It is well known that DNA damage can cause apoptosis. However, whether apoptosis and its metabolites contribute to DNA repair is largely unknown. In this study, we found that apoptosis‐deficient Fasmut and Bim−/− mice show significantly elevated DNA damage and premature cellular senescence, along with a significantly reduced number of 16,000 g apoptotic vesicles (apoVs). Intravenous infusion of mesenchymal stromal cell (MSC)‐derived 16,000 g apoVs rescued the DNA damage and premature senescence in Fasmut and Bim−/− mice. Moreover, a sublethal dose of radiation exposure caused more severe DNA damage, reduced survival rate, and loss of body weight in Fasmut mice than in wild‐type mice, which can be recovered by the infusion of MSC‐apoVs. Mechanistically, we showed that apoptosis can assemble multiple nuclear DNA repair enzymes, such as the full‐length PARP1, into 16,000 g apoVs. These DNA repair components are directly transferred by 16,000 g apoVs to recipient cells, leading to the rescue of DNA damage and elimination of senescent cells. Finally, we showed that embryonic stem cell‐derived 16,000 g apoVs have superior DNA repair capacity due to containing a high level of nuclear DNA repair enzymes to rescue lethal dose‐irradiated mice. This study uncovers a previously unknown role of 16,000 g apoVs in safeguarding tissues from DNA damage and demonstrates a strategy for using stem cell‐derived apoVs to ameliorate irradiation‐induced DNA damage.

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“…22 When mtDNA is damaged or stressed, it can be released from mitochondria into the cytosol and acts as damage-associated molecular patterns (DAMPs) to stimulate the innate immune response. 23,24 Herein, the cytosolic DNA sensor of cyclic GMP-AMP synthase (cGAS) is activated and promotes the stimulator of interferon genes (STING), TANK binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3) signaling to elevate type I interferon (IFN) and other pro-inflammatory cytokines responses. 25 Increasing evidence suggests that mitochondria and mtDNA are critically vulnerable to environmental pollutants, and previous studies have provided novel insight into the health risk implicated in mitochondrial toxicity of DBP.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Stress-Mediated Health Risk to Dibutyl Phthalate Contamination on Zebrafish (Danio rerio) at Early Life Stage

Fan,

Zhang,

Hou

et al. 2024

Environ. Sci. Technol.

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Plastics contaminations are found globally and fit the exposure profile of the planetary boundary threat. The plasticizer of dibutyl phthalate (DBP) leaching has occurred and poses a great threat to human health and the ecosystem for decades, and its toxic mechanism needs further comprehensive elucidation. In this study, environmentally relevant levels of DBP were used for exposure, and the developmental process, oxidative stress, mitochondrial ultrastructure and function, mitochondrial DNA (mtDNA) instability and release, and mtDNA-cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway with inflammatory responses were measured in zebrafish at early life stage. Results showed that DBP exposure caused developmental impairments of heart rate, hatching rate, body length, and mortality in zebrafish embryo. Additionally, the elevated oxidative stress damaged mitochondrial ultrastructure and function and induced oxidative damage to the mtDNA with mutations and instability of replication, transcription, and DNA methylation. The stressed mtDNA leaked into the cytosol and activated the cGAS-STING signaling pathway and inflammation, which were ameliorated by co-treatment with DBP and mitochondrial reactive oxygen species (ROS) scavenger, inhibitors of cGAS or STING. Furthermore, the larval results suggest that DBP-induced mitochondrial toxicity of energy disorder and inflammation were involved in the developmental defects of impaired swimming capability. These results enhance the interpretation of mtDNA stress-mediated health risk to environmental contaminants and contribute to the scrutiny of mitochondrial toxicants.

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The fate of damaged mitochondrial DNA in the cell

Cited by 35 publications

References 84 publications

LC-HRMS analysis of corn mint Mentha arvensis L. for anticancer activity against triple-negative breast cancer targeting inflammatory and apoptosis signaling pathways

LC-HRMS analysis of corn mint Mentha arvensis L. for anticancer activity against triple-negative breast cancer targeting inflammatory and apoptosis signaling pathways

Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence

Mitochondrial DNA Stress-Mediated Health Risk to Dibutyl Phthalate Contamination on Zebrafish (Danio rerio) at Early Life Stage

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