ArticleCell death and differentiation2024
SIRT5-mediated ME2 desuccinylation promotes cancer growth by enhancing mitochondrial respiration.
Article in Cell death and differentiation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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.
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Who cites it
47 citing papers in PubMed, 55 citations in OpenAlex.
- DLST Succinylation-Mediated Mitochondrial Metabolic Remodeling and Cuproptosis Resistance Promote Malignant Progression of Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer-associated adipocytes: metabolic reprogramming, crosstalk and therapeutic implications in tumor progression.Signal transduction and targeted therapy · 2026Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism.Nature communications · 2026Article
- Elevated BACH1 Contributes to Mitochondrial Succinylome Remodeling and Trophoblast Bioenergetic Dysfunction in Preeclampsia.Antioxidants (Basel, Switzerland) · 2026Article
- SIRT5-dependent regulation of ASL controls arginine metabolism and T cell function.bioRxiv : the preprint server for biology · 2026Article
- Glucose starvation induces fumarate hydratase succinylation and inhibits ferroptosis to maintain colon cancer cell proliferation.Cell death & disease · 2026Article
- Mechanistic and functional integration of sirtuin deacylases: from substrate specificity to biological outcomes.Glycoconjugate journal · 2026Review
- Targeting ADAR1 lactylation activates innate immune and overcomes chemoresistance in ovarian cancer.Cell death and differentiation · 2026Article
- Beyond deacetylation: crosstalk mechanisms and context-dependent regulation of sirtuin non-classical enzymatic functions in disease.Molecular medicine (Cambridge, Mass.) · 2026Review
- HDAC8-mediated CAPZB desuccinylation enhances cytoskeleton remodeling to promote idiopathic pulmonary fibrosis.Communications biology · 2026Article
- Unveiling the importance of SIRT5 for cardiac health and disease in an era of increasing longevity.GeroScience · 2026Review
- Malic enzyme 2 suppresses PINK1-Parkin-mediated mitophagy by stabilizing ATAD3A via competitive interaction with TRIM25.Cell death & disease · 2026Article
- Succinylation: A Functional Nexus Between Metabolic Reprogramming and Epigenetic Modifications in Cancer.Molecules (Basel, Switzerland) · 2026Review
- Succinylation in cancer immunotherapy: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- Review
- SIRT5-mediated regulation of BMP2 succinylation enhances osteogenic differentiation of BMSCs and promotes tibial fracture healing.Stem cell research & therapy · 2025Article
- RAB22A triggers intercellular chemoresistance transmission in colorectal cancer by promoting exosome release via the PKM2-pSNAP23 axis.Oncogene · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Mitochondrial malic enzyme 2 (ME2), which catalyzes the conversion of malate to pyruvate, is frequently upregulated during tumorigenesis and is a potential target for cancer therapy. However, the regulatory mechanism underlying ME2 activity is largely unknown. In this study, we demonstrate that ME2 is highly expressed in human colorectal cancer (CRC) tissues, and that ME2 knockdown inhibits the proliferation of CRC cells. Furthermore, we reveal that ME2 is succinylated and identify Sirtuins 5 (SIRT5) as an ME2 desuccinylase. Glutamine deprivation directly enhances the interaction of SIRT5 with ME2 and thus promotes SIRT5-mediated desuccinylation of ME2 at lysine 346, activating ME2 enzymatic activity. Activated ME2 significantly enhances mitochondrial respiration, thereby counteracting the effects of glutamine deprivation and supporting cell proliferation and tumorigenesis. Additionally, the levels of succinylated ME2 at K346 and SIRT5 in CRC tissues, which are negatively correlated, are associated with patient prognosis. These observations suggest that SIRT5-catalyzed ME2 desuccinylation is a key signaling event through which cancer cells maintain mitochondrial respiration and promote CRC progression under glutamine deficiency conditions, offering the possibility of targeting SIRT5-mediated ME2 desuccinylation for CRC treatment.
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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.