ArticleThe Journal of clinical investigation2024
A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Article
- Review
- Variant-specific SF3B1 mutations drive distinct splicing and mitochondrial dysfunction in myelodysplastic neoplasms.Human genomics · 2026Article
- Novel and emerging therapeutic strategies for clonal hematopoiesis.Haematologica · 2026Review
- Mitophagy-driven prognosis in pediatric acute myeloid leukemia: a new frontier.Scientific reports · 2026Article
- SRSF2 mutations drive daunorubicin resistance in acute myeloid leukemia via THBS1 stabilization.Journal of experimental & clinical cancer research : CR · 2026Article
- Myelodysplastic syndrome progress to acute myeloid leukemia: new insights and updates.Frontiers in immunology · 2026Review
- Unlocking the undruggable spliceosome: generative AI and structural dynamics in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Hepatocyte mitochondrial NADNature metabolism · 2025Article
- The role of ASXL1, SRSF2, and EZH2 mutations in chromatin dysregulation of myelodysplastic neoplasia and acute myeloid leukemia.Leukemia · 2025Review
- Review
- Genetic variation reveals a homeotic long noncoding RNA that modulates human hematopoietic stem cells.bioRxiv : the preprint server for biology · 2025Article
- Decoding the diagnostic biomarkers of mitochondrial dysfunction related gene variants in pediatric T cell acute lymphoblastic leukemia.Scientific reports · 2025Article
- Myelodysplastic Neoplasms (MDS): Pathogenesis and Therapeutic Prospects.Biomolecules · 2025Review
- Mitochondrial quality control in hematopoietic stem cells: mechanisms, implications, and therapeutic opportunities.Stem cell research & therapy · 2025Review
- Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2025Review
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
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Abstract
Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts the splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. We also identified a mitochondrial surveillance mechanism by which mitochondrial dysfunction modifies splicing of the mitophagy activator PINK1 to remove a poison intron, increasing the stability and abundance of PINK1 mRNA and protein. SRSF2P95H-induced mitochondrial dysfunction increased PINK1 expression through this mechanism, which is essential for survival of SRSF2P95H/+ cells. Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis in SRSF2P95H/+ cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress through PINK1 splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability in SRSF2P95H mutant MDS and AML.
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