ArticleThe EMBO journal2024
SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 27 citations in OpenAlex.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- SLIRP maintains energy metabolism homeostasis in colorectal cancer by stabilizing mitochondrial-encoded mRNAs.British journal of cancer · 2026Article
- Targeting POLRMT-driven epigenetic remodeling of Wnt/β-catenin to eradicate colorectal cancer stem cell proliferation.Cell death and differentiation · 2026Article
- TCA-controlled histone succinylation identifies IDH3B as a prognostic and therapeutic target in AML.Clinical epigenetics · 2026Article
- MoCox6 is a regulator of mitophagy and a druggable target in Magnaporthe oryzae.Nature microbiology · 2026Article
- Re-evaluating the rationale for targeting oxidative phosphorylation in acute myeloid leukemia.The Biochemical journal · 2026Review
- Article
- Role of Succinate Dehydrogenase in Age-Related Th17 Inflammation.Aging cell · 2026Article
- Succinylation: A Functional Nexus Between Metabolic Reprogramming and Epigenetic Modifications in Cancer.Molecules (Basel, Switzerland) · 2026Review
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- Succinylation: novel molecular mechanisms and prospects for targeted therapy in liver diseases.Frontiers in molecular biosciences · 2026Review
- Combined machine learning identification and experimental validation of NDUFS8 and SUCLG1 as potential biomarkers for mechanical asphyxia.Frontiers in medicine · 2026Article
- Targeting cuproptosis for treatment and prognostic assessment in endometrial cancer.Cancer cell international · 2025Review
- Review
- Thyroid hormones contribute to JAK/STAT pathway abnormal activation, promoting T-cell lymphoma dissemination.Blood advances · 2025Article
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Acyl post-translational modification of proteins by metabolites in cancer cells.Cell death discovery · 2025Review
- SIRT5 Alleviates Apoptosis of Vascular Endothelial Cells Under Simulated Microgravity via Desuccinylation of ERO1A.International journal of molecular sciences · 2025Article
- Lysine succinylation precisely controls normal erythropoiesis.Haematologica · 2025Article
- Succinyl-coenzyme A: a key metabolite and succinyl group donor in erythropoiesis.Haematologica · 2025Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Mitochondria are cellular powerhouses that generate energy through the electron transport chain (ETC). The mitochondrial genome (mtDNA) encodes essential ETC proteins in a compartmentalized manner, however, the mechanism underlying metabolic regulation of mtDNA function remains unknown. Here, we report that expression of tricarboxylic acid cycle enzyme succinate-CoA ligase SUCLG1 strongly correlates with ETC genes across various TCGA cancer transcriptomes. Mechanistically, SUCLG1 restricts succinyl-CoA levels to suppress the succinylation of mitochondrial RNA polymerase (POLRMT). Lysine 622 succinylation disrupts the interaction of POLRMT with mtDNA and mitochondrial transcription factors. SUCLG1-mediated POLRMT hyposuccinylation maintains mtDNA transcription, mitochondrial biogenesis, and leukemia cell proliferation. Specifically, leukemia-promoting FMS-like tyrosine kinase 3 (FLT3) mutations modulate nuclear transcription and upregulate SUCLG1 expression to reduce succinyl-CoA and POLRMT succinylation, resulting in enhanced mitobiogenesis. In line, genetic depletion of POLRMT or SUCLG1 significantly delays disease progression in mouse and humanized leukemia models. Importantly, succinyl-CoA level and POLRMT succinylation are downregulated in FLT3-mutated clinical leukemia samples, linking enhanced mitobiogenesis to cancer progression. Together, SUCLG1 connects succinyl-CoA with POLRMT succinylation to modulate mitochondrial function and cancer development.
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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.