ArticleBlood2015
Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 66 citations in OpenAlex.
- Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026Review
- Small but mighty: mitochondrial DNA at the centre of retrograde signalling.Cell communication and signaling : CCS · 2026Review
- Expression profiling reveals coordinated dysregulation of autophagy-associated proteins in marginal zone lymphoma and therapeutic implications.Oncology letters · 2026Article
- Respiration defects limit serine synthesis required for lung cancer growth and survival.Nature communications · 2025Article
- The involvement of mitochondria in erythrocyte pathology and diseases: from mechanisms to therapeutic strategies.Clinical and experimental medicine · 2025Review
- The Role of mtDNA Mutations in Atherosclerosis: The Influence of Mitochondrial Dysfunction on Macrophage Polarization.International journal of molecular sciences · 2025Review
- Somatic mtDNA mutation burden shapes metabolic plasticity in leukemogenesis.Science advances · 2025Article
- Mitochondrial DNA alterations in precision oncology: Emerging roles in diagnostics and therapeutics.Clinics (Sao Paulo, Brazil) · 2025Review
- Mitochondrial regulation of erythropoiesis in homeostasis and disease.British journal of haematology · 2024Review
- Saracatinib prompts hemin-induced K562 erythroid differentiation but suppresses erythropoiesis of hematopoietic stem cells.Human cell · 2024Article
- The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia.Cancer research · 2024Article
- Mitochondrial Dysfunction and Protein Homeostasis in Aging: Insights from a Premature-Aging Mouse Model.Biomolecules · 2024Article
- Immunoregulation role of the erythroid cells.Frontiers in immunology · 2024Review
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications.Signal transduction and targeted therapy · 2023Review
- Human erythroid differentiation requires VDAC1-mediated mitochondrial clearance.Haematologica · 2022Article
- DNA Polymerase Gamma Recovers Mitochondrial Function and Inhibits Vascular Calcification by Interacted with p53.International journal of biological sciences · 2022Article
- FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway.Autophagy · 2021Article
- The Association of Mitochondrial Copy Number With Sarcopenia in Adult Survivors of Childhood Cancer.Journal of the National Cancer Institute · 2021Article
- Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?Stem cell reviews and reports · 2020Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Somatic mitochondrial DNA (mtDNA) mutations contribute to the pathogenesis of age-related disorders, including myelodysplastic syndromes (MDS). The accumulation of mitochondria harboring mtDNA mutations in patients with these disorders suggests a failure of normal mitochondrial quality-control systems. The mtDNA-mutator mice acquire somatic mtDNA mutations via a targeted defect in the proofreading function of the mtDNA polymerase, PolgA, and develop macrocytic anemia similar to that of patients with MDS. We observed an unexpected defect in clearance of dysfunctional mitochondria at specific stages during erythroid maturation in hematopoietic cells from aged mtDNA-mutator mice. Mechanistically, aberrant activation of mechanistic target of rapamycin signaling and phosphorylation of uncoordinated 51-like kinase (ULK) 1 in mtDNA-mutator mice resulted in proteasome-mediated degradation of ULK1 and inhibition of autophagy in erythroid cells. To directly evaluate the consequence of inhibiting autophagy on mitochondrial function in erythroid cells harboring mtDNA mutations in vivo, we deleted Atg7 from erythroid progenitors of wild-type and mtDNA-mutator mice. Genetic disruption of autophagy did not cause anemia in wild-type mice but accelerated the decline in mitochondrial respiration and development of macrocytic anemia in mtDNA-mutator mice. These findings highlight a pathological feedback loop that explains how dysfunctional mitochondria can escape autophagy-mediated degradation and propagate in cells predisposed to somatic mtDNA mutations, leading to disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.