ArticleThe Journal of clinical investigation2010
Prkdc participates in mitochondrial genome maintenance and prevents Adriamycin-induced nephropathy in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 105 citations in OpenAlex.
- Resistance to doxorubicin-induced proteinuria and proteolytic activation of ENaC in 129S2/SvPas mice.Physiological reports · 2025Article
- Adriamycin-induced nephropathy models: elucidating CKD pathophysiology and advancing therapeutic strategies.Experimental animals · 2025Review
- Low-dose radiation ameliorates doxorubicin-induced renal injury via reducing oxidative stress and protecting mitochondrial function.PloS one · 2025Article
- Article
- Development and Characterization of a Novel FVB-Genes · 2024Article
- Differences in susceptibility to ADR nephropathy among C57BL/6 substrains.Experimental animals · 2023Article
- Female but Not Male Mice Deficient in Soluble IgM Are Susceptible to Chemically Induced Glomerular Injury.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Susceptibility to adriamycin-induced hepatotoxicity in mice depends on PRKDC polymorphism.The Journal of veterinary medical science · 2023Article
- Induce male sterility by CRISPR/Cas9-mediated mitochondrial genome editing in tobacco.Functional & integrative genomics · 2023Article
- Molecular and Pathological Analyses of IARS1-Deficient Mice: An IARS Disorder Model.International journal of molecular sciences · 2023Article
- DNA-PKcs and ATM modulate mitochondrial ADP-ATP exchange as an oxidative stress checkpoint mechanism.The EMBO journal · 2023Article
- Genetic background strongly influences the transition to chronic kidney disease of adriamycin nephropathy in mice.Experimental animals · 2023Article
- Protective effect of the tunneling nanotube-TNFAIP2/M-sec system on podocyte autophagy in diabetic nephropathy.Autophagy · 2023Article
- Anti-ANGPTL3-FLD monoclonal antibody treatment ameliorates podocyte lesions through attenuating mitochondrial damage.Cell death & disease · 2022Article
- Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice.Scientific reports · 2022Article
- Adriamycin-Induced Nephropathy is Robust in N and Modest in J Substrain of C57BL/6.Frontiers in cell and developmental biology · 2022Article
- Essential role of DNA-PKcs and plasminogen for the development of doxorubicin-induced glomerular injury in mice.Disease models & mechanisms · 2021Article
- Dysregulated Dynein-Mediated Trafficking of Nephrin Causes INF2-related Podocytopathy.Journal of the American Society of Nephrology : JASN · 2021Article
- Synaptopodin Is Dispensable for Normal Podocyte Homeostasis but Is Protective in the Context of Acute Podocyte Injury.Journal of the American Society of Nephrology : JASN · 2020Article
- MicroRNA‑145 promotes the apoptosis of leukemic stem cells and enhances drug‑resistant K562/ADM cell sensitivity to adriamycin via the regulation of ABCE1.International journal of molecular medicine · 2020Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Adriamycin (ADR) is a commonly used chemotherapeutic agent that also produces significant tissue damage. Mutations to mitochondrial DNA (mtDNA) and reductions in mtDNA copy number have been identified as contributors to ADR-induced injury. ADR nephropathy only occurs among specific mouse inbred strains, and this selective susceptibility to kidney injury maps as a recessive trait to chromosome 16A1-B1. Here, we found that sensitivity to ADR nephropathy in mice was produced by a mutation in the Prkdc gene, which encodes a critical nuclear DNA double-stranded break repair protein. This finding was confirmed in mice with independent Prkdc mutations. Overexpression of Prkdc in cultured mouse podocytes significantly improved cell survival after ADR treatment. While Prkdc protein was not detected in mitochondria, mice with Prkdc mutations showed marked mtDNA depletion in renal tissue upon ADR treatment. To determine whether Prkdc participates in mtDNA regulation, we tested its genetic interaction with Mpv17, which encodes a mitochondrial protein mutated in human mtDNA depletion syndromes (MDDSs). While single mutant mice were asymptomatic, Prkdc/Mpv17 double-mutant mice developed mtDNA depletion and recapitulated many MDDS and ADR injury phenotypes. These findings implicate mtDNA damage in the development of ADR toxicity and identify Prkdc as a MDDS modifier gene and a component of the mitochondrial genome maintenance pathway.
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