ArticlePLoS genetics2022
Mice lacking the mitochondrial exonuclease MGME1 develop inflammatory kidney disease with glomerular dysfunction.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Cardiomyocyte-intrinsic somatic mtDNA mutations induce an OXPHOS-dependent immune response and promote progressive heart failure.Science advances · 2026Article
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- Host mitochondrial DNA in bacterial pathogenesis: Friend, Foe, or Both?Archives of microbiology · 2026Review
- Mitochondrial DNA copy number as a genetic determinant of renal function: insights from bidirectional Mendelian randomization.Renal failure · 2025Article
- Glutathionylated DNA adducts accumulate in mitochondrial DNA and are regulated by AP endonuclease 1 and tyrosyl-DNA phosphodiesterase 1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Nuclease-induced stepwise photodropping (NISP) to precisely investigate single-stranded DNA degradation behaviors of exonucleases and endonucleases.Nucleic acids research · 2024Article
- Causal network perturbation analysis identifies known and novel type-2 diabetes driver genes.bioRxiv : the preprint server for biology · 2024Article
- Structural basis of how MGME1 processes DNA 5' ends to maintain mitochondrial genome integrity.Nucleic acids research · 2024Article
- Recent Advances in Proteinuric Kidney Disease/Nephrotic Syndrome: Lessons from Knockout/Transgenic Mouse Models.Biomedicines · 2023Review
- Key Amino Acid Residues of Mitochondrial Transcription Factor A Synergize with Abasic (AP) Site Dynamics To Facilitate AP-Lyase Reactions.ACS chemical biology · 2023Article
- MGME1 associates with poor prognosis and is vital for cell proliferation in lower-grade glioma.Aging · 2023Article
- Roles of Mitochondrial DNA Damage in Kidney Diseases: A New Biomarker.International journal of molecular sciences · 2022Review
- The immune system as a driver of mitochondrial disease pathogenesis: a review of evidence.Orphanet journal of rare diseases · 2022Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial DNA (mtDNA) maintenance disorders are caused by mutations in ubiquitously expressed nuclear genes and lead to syndromes with variable disease severity and tissue-specific phenotypes. Loss of function mutations in the gene encoding the mitochondrial genome and maintenance exonuclease 1 (MGME1) result in deletions and depletion of mtDNA leading to adult-onset multisystem mitochondrial disease in humans. To better understand the in vivo function of MGME1 and the associated disease pathophysiology, we characterized a Mgme1 mouse knockout model by extensive phenotyping of ageing knockout animals. We show that loss of MGME1 leads to de novo formation of linear deleted mtDNA fragments that are constantly made and degraded. These findings contradict previous proposal that MGME1 is essential for degradation of linear mtDNA fragments and instead support a model where MGME1 has a critical role in completion of mtDNA replication. We report that Mgme1 knockout mice develop a dramatic phenotype as they age and display progressive weight loss, cataract and retinopathy. Surprisingly, aged animals also develop kidney inflammation, glomerular changes and severe chronic progressive nephropathy, consistent with nephrotic syndrome. These findings link the faulty mtDNA synthesis to severe inflammatory disease and thus show that defective mtDNA replication can trigger an immune response that causes age-associated progressive pathology in the kidney.
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