ArticleCell metabolism2021
Malic enzyme 2 connects the Krebs cycle intermediate fumarate to mitochondrial biogenesis.
Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 88 citations in OpenAlex.
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- Protein arginine methyltransferases as metabolic regulators: many roles beyond cancer.Science China. Life sciences · 2026Review
- A cryptic allosteric pocket shapes isoform-selective inhibition of human malic enzymes.Protein science : a publication of the Protein Society · 2026Article
- Scanning central carbon metabolism: a HILIC-HR-TOF-MS metabolome method.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- Malic enzyme 2 suppresses PINK1-Parkin-mediated mitophagy by stabilizing ATAD3A via competitive interaction with TRIM25.Cell death & disease · 2026Article
- Chloroplast Stress Signals Orchestrate Epidermis-Specific Remodeling of Mitochondria and ER Under High Light.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrative Transcriptomic Analysis Identifies Novel Mitochondrial Gene Targets in Parkinson's Disease.Molecular neurobiology · 2026Article
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
- MitoCommun: a database for decoding mitochondrial communication networks.BMC genomics · 2026Article
- Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- PGC-1α Transcriptionally Regulated by ChREBP Mitigates Neuropathic Pain Through Promoting Microglial Fatty Acid Oxidation and Anti-Inflammatory Response.CNS neuroscience & therapeutics · 2026Article
- Targeting the PRMT1 axis in cancer: from epigenetic plasticity to contextual therapeutic interventions.Frontiers in oncology · 2026Review
- Methylmalonate accumulation contributes to myocardial vulnerability post-reperfusion: a novel therapeutic target and prognostic biomarker.BMC medicine · 2025Article
- Review
- CYP4F11 promotes lung cancer progression through the miR-195/ME2 pathway.Frontiers of medicine · 2025Article
- Revealing the adaptive metabolic differences of different sheep breeds in plateau areas based on the Gut-Cardiac axis.BMC genomics · 2025Article
- Mitochondrial Network Fragmentation Leads to Dysfunction of Macrophages DuringPathogens (Basel, Switzerland) · 2025Article
- α-Methyltryptophan mitigates cognitive impairment in db/db mice: involvement of gut-brain metabolic remodeling.Nutrition & metabolism · 2025Article
- Dimethyl fumarate reprograms cervical cancer cells to enhance antitumor immunity by activating mtDNA-cGAS-STING pathway.Journal of biomedical science · 2025Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Mitochondria have an independent genome (mtDNA) and protein synthesis machinery that coordinately activate for mitochondrial generation. Here, we report that the Krebs cycle intermediate fumarate links metabolism to mitobiogenesis through binding to malic enzyme 2 (ME2). Mechanistically, fumarate binds ME2 with two complementary consequences. First, promoting the formation of ME2 dimers, which activate deoxyuridine 5'-triphosphate nucleotidohydrolase (DUT). DUT fosters thymidine generation and an increase of mtDNA. Second, fumarate-induced ME2 dimers abrogate ME2 monomer binding to mitochondrial ribosome protein L45, freeing it for mitoribosome assembly and mtDNA-encoded protein production. Methylation of the ME2-fumarate binding site by protein arginine methyltransferase-1 inhibits fumarate signaling to constrain mitobiogenesis. Notably, acute myeloid leukemia is highly dependent on mitochondrial function and is sensitive to targeting of the fumarate-ME2 axis. Therefore, mitobiogenesis can be manipulated in normal and malignant cells through ME2, an unanticipated governor of mitochondrial biomass production that senses nutrient availability through fumarate.
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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.