MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission

The modification of proteins by the small ubiquitin‐like modifier (SUMO) is known to regulate an increasing array of cellular processes. SUMOylation of the mitochondrial fission GTPase dynamin‐related protein 1 (DRP1) stimulates mitochondrial fission, suggesting that SUMOylation has an important function in mitochondrial dynamics. The conjugation of SUMO to its substrates requires a regulatory SUMO E3 ligase; however, so far, none has been functionally associated with the mitochondria. By using biochemical assays, overexpression and RNA interference experiments, we characterized the mitochondrial‐anchored protein ligase (MAPL) as the first mitochondrial‐anchored SUMO E3 ligase. Furthermore, we show that DRP1 is a substrate for MAPL, providing a direct link between MAPL and the fission machinery. Importantly, the large number of unidentified mitochondrial SUMO targets suggests a global role for SUMOylation in mitochondrial function, placing MAPL as a crucial component in the regulation of multiple conjugation events.

• Publication year

  2009

• Venue

  EMBO Reports

• Publication date

  2009-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/embor.2009.86PMID 19407830PMCID PMC2727426
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers.

  2008influential reference
• Genome-Wide and Functional Annotation of Human E3 Ubiquitin Ligases Identifies MULAN, a Mitochondrial E3 that Regulates the Organelle's Dynamics and Signaling

  2008cited by this paper
• The type I TGF-β receptor is covalently modified and regulated by sumoylation

  2008cited by this paper
• Protein interactions in the sumoylation cascade – lessons from X‐ray structures

  2008influential reference
• Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death

  2007influential reference
• The role of karyopherins in the regulated sumoylation of septins

  2007cited by this paper
• Emerging extranuclear roles of protein SUMOylation in neuronal function and dysfunction

  2007cited by this paper
• Concepts in sumoylation: a decade on

  2007cited by this paper
• PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing.

  2007cited by this paper
• The SUMO protease SENP5 is required to maintain mitochondrial morphology and function

  2007cited by this paper
• The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division

  2007cited by this paper
• Regulation of protein tyrosine phosphatase 1B by sumoylation

  2007cited by this paper
• The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis.

  2006cited by this paper
• MARCH‐V is a novel mitofusin 2‐ and Drp1‐binding protein able to change mitochondrial morphology

  2006cited by this paper
• A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics

  2006cited by this paper
• Sumoylation silences the plasma membrane leak K+ channel K2P1.

  2005cited by this paper
• Activated Mitofusin 2 Signals Mitochondrial Fusion, Interferes with Bax Activation, and Reduces Susceptibility to Radical Induced Depolarization*[boxs]

  2005cited by this paper
• Sumo1 conjugates mitochondrial substrates and participates in mitochondrial fission.

  2004influential reference
• Faculty Opinions recommendation of The polycomb protein Pc2 is a SUMO E3.

  2003cited by this paper
• Plant RanGAPs are localized at the nuclear envelope in interphase and associated with microtubules in mitotic cells.

  2002cited by this paper
• The nucleoporin RanBP2 has SUMO1 E3 ligase activity.

  2002cited by this paper
• Involvement of PIAS1 in the sumoylation of tumor suppressor p53.

  2001cited by this paper
• Cell Cycle–Regulated Attachment of the Ubiquitin-Related Protein Sumo to the Yeast Septins

  1999cited by this paper

• SUMOylation and anticancer drug resistance.

  2026cites this paper
• SUMO-2/3 modification of PINK1 restrains basal mitophagy through MAPL-dependent regulation of mitochondrial surveillance

  2026cites this paper
• Definition of the human mitochondrial TOM interactome reveals TRABD as new interacting protein.

  2025cites this paper
• 17-beta estradiol prevents cardiac myocyte hypertrophy by regulating mitochondrial E3 ubiquitin ligase 1

  2025cites this paper
• Important regulatory role of mitophagy in diabetic microvascular complications

  2025cites this paper
• NIPSNAP1 and NIPSNAP2 facilitate healthy aging independent of mitophagy.

  2025cites this paper
• Organelle regulation of SUMOylation: regulatory mechanisms and therapeutic application.

  2025cites this paper
• Mitophagy: A key regulator in the pathophysiology and treatment of spinal cord injury

  2025cites this paper
• Intricate role of DRP1 and associated mitochondrial fission signaling in carcinogenesis and cancer progression.

  2025cites this paper
• The critical role of mitophagy in cell senescence-mediated pulmonary fibrosis and potential therapeutic strategies

  2025cites this paper
• Simulated Microgravity-Induced Changes in SUMOylation and Protein Expression in Saccharomyces cerevisiae

  2025cites this paper
• The mitochondrial E3 ligase MAPL SUMOylates Drp1 to facilitate mitochondrial fission in intervertebral disc degeneration

  2025cites this paper
• DNA repair pathways in the mitochondria.

  2025cites this paper
• SENP6 Maintains Mitochondrial Homeostasis by Regulating Mitochondrial Protein Import Through deSUMOylation of TOM40

  2025cites this paper
• Novel insights into genetic associations and drug targets of mitochondria-associated proteins with major depressive disorder.

  2025cites this paper
• MAPL regulates gasdermin-mediated release of mtDNA from lysosomes to drive pyroptotic cell death

  2025cites this paper
• MTFP1 controls mitochondrial fusion to regulate inner membrane quality control and maintain mtDNA levels.

  2024cites this paper
• Mitochondrial dynamics in pulmonary disease: Implications for the potential therapeutics

  2024cites this paper
• VPS35 and retromer dysfunction in Parkinson's disease

  2024cites this paper
• SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation

  2024cites this paper
• Spray-type modifications: an emerging paradigm in post-translational modifications.

  2024cites this paper
• Inactivation of mitochondrial MUL1 E3 ubiquitin ligase deregulates mitophagy and prevents diet-induced obesity in mice

  2024cites this paper
• Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response

  2024cites this paper
• Comparative transcriptome profiling across 9 tissues in 2 pika species provides new insights and resources to interpret plateau adaptation

  2024cites this paper
• Recent insights into the control of mitochondrial fission.

  2024cites this paper
• Inhibition of K63 ubiquitination by G-Protein pathway suppressor 2 (GPS2) regulates mitochondria-associated translation

  2024cites this paper
• The interplay between mitochondrial dynamics and autophagy: From a key homeostatic mechanism to a driver of pathology.

  2024cites this paper
• Deletion of MAPL ameliorates septic cardiomyopathy by mitigating mitochondrial dysfunction

  2024cites this paper
• SUMOylation of MFF coordinates fission complexes to promote stress-induced mitochondrial fragmentation

  2024cites this paper
• NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia

  2024cites this paper
• Mitochondrial quality control: the real dawn of intervertebral disc degeneration?

  2024cites this paper
• Monoclonal antibody‐based systematic identification of SUMO1‐modification sites reveals TFII‐I SUMOylation is involved in tumor growth

  2023cites this paper
• Effects of Mdivi‐1 on Extending the Golden Treatment Time following Hemorrhagic Shock in Hot Environment in Rats

  2023cites this paper
• Convergent and divergent mechanisms of peroxisomal and mitochondrial division

  2023cites this paper
• Myristate induces mitochondrial fragmentation and cardiomyocyte hypertrophy through mitochondrial E3 ubiquitin ligase MUL1

  2023influential citation
• Mitochondrial outer membrane integrity regulates a ubiquitin-dependent NF-κB inflammatory response

  2023cites this paper
• MAPL loss dysregulates bile and liver metabolism in mice

  2023influential citation
• Mitochondrial dynamics in macrophages: divide to conquer or unite to survive?

  2023cites this paper
• The role of mitochondrial dynamics in disease

  2023cites this paper
• Parkinson’s genes orchestrate pyroptosis through selective trafficking of mtDNA to leaky lysosomes

  2023cites this paper
• Importance of mitochondrial quality control and its role in pathophysiology

  2023cites this paper
• Function and regulation of ubiquitin-like SUMO system in heart

  2023cites this paper
• The mitophagy pathway and its implications in human diseases

  2023cites this paper
• Control of Mitochondrial Activity by the Ubiquitin Code in Health and Cancer

  2023cites this paper
• Role of the Mitochondrial E3 Ubiquitin Ligases as Possible Therapeutic Targets in Cancer Therapy

  2023cites this paper
• Mitochondrial mechanisms in Alzheimer's disease: quest for therapeutics.

  2023cites this paper
• Protein ubiquitination in plant peroxisomes.

  2022cites this paper
• SUMOylation of SYNJ2BP-COX16 promotes breast cancer progression through DRP1-mediated mitochondrial fission.

  2022cites this paper
• SUMOylation and Major Depressive Disorder

  2022cites this paper
• Regulation of Metabolism by Mitochondrial MUL1 E3 Ubiquitin Ligase

  2022cites this paper
• Mitochondrial-derived vesicles: Gatekeepers of mitochondrial response to oxidative stress.

  2022cites this paper
• Identification and expression analysis of a new small ubiquitin-like modifier from Taenia pisiformis.

  2022cites this paper
• Role of Mitochondrial Dynamics in Cocaine’s Neurotoxicity

  2022cites this paper
• Regulation of mitochondrial dysfunction induced cell apoptosis is a potential therapeutic strategy for herbal medicine to treat neurodegenerative diseases

  2022influential citation
• Podocyte Injury in Diabetic Kidney Disease: A Focus on Mitochondrial Dysfunction

  2022cites this paper
• SUMOylation of ABCD3 restricts bile acid synthesis and regulates metabolic homeostasis

  2022cites this paper
• Mitochondrial E3 ubiquitin ligase 1 (MUL1) as a novel therapeutic target for diseases associated with mitochondrial dysfunction

  2022cites this paper
• AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology

  2022cites this paper
• Role of SUMOylation in Neurodegenerative Diseases

  2022cites this paper
• Mitochondrial dynamics and oxidative phosphorylation as targets in cancer.

  2022cites this paper
• SUMOylation targeting mitophagy in cardiovascular diseases

  2022cites this paper
• High water temperature raised the requirements of methionine for spotted seabass (Lateolabrax maculatus)

  2022cites this paper
• Mechanistic and therapeutic role of Drp1 in the pathogenesis of stroke.

  2022cites this paper
• Mitochondrial dynamics involves molecular and mechanical events in motility, fusion and fission

  2022cites this paper
• Selective localization of Mfn2 near PINK1 enables its preferential ubiquitination by Parkin on mitochondria

  2022cites this paper
• Mitochondrial proteotoxicity: implications and ubiquitin-dependent quality control mechanisms

  2022cites this paper
• Regulation of PRKN-independent mitophagy

  2021influential citation
• Mitochondrial Dynamics: Molecular Mechanisms, Related Primary Mitochondrial Disorders and Therapeutic Approaches

  2021cites this paper
• UBXN7 cofactor of CRL3KEAP1 and CRL2VHL ubiquitin ligase complexes mediates reciprocal regulation of NRF2 and HIF-1α proteins.

  2021cites this paper
• Mitophagy Impairment in Neurodegenerative Diseases: Pathogenesis and Therapeutic Interventions.

  2021cites this paper
• SUMOylation of mitofusins: a potential mechanism for perinuclear mitochondrial congression in cells treated with mitochondrial stressors.

  2021cites this paper
• Mitophagy Disequilibrium, a Prominent Pathological Mechanism in Metabolic Heart Diseases

  2021cites this paper
• Proteomic Identification of an Endogenous Synaptic SUMOylome in the Developing Rat Brain

  2021cites this paper
• Balancing life and death: BCL‐2 family members at diverse ER–mitochondrial contact sites

  2021cites this paper
• Mitophagy in sarcopenic muscle and practical recommendations for exercise training

  2021cites this paper
• Mitochondria and Their Cell Hosts: Best of Frenemies

  2021cites this paper
• Targeting adaptive cellular responses to mitochondrial bioenergetic deficiencies in human disease

  2021cites this paper
• Mitochondrial biogenesis and mitophagy

  2021cites this paper
• Mitochondria Dynamics: Definition, Players and Associated Disorders

  2021cites this paper
• Membrane compartmentalisation of the ubiquitin system.

  2021cites this paper
• Mff oligomerization is required for Drp1 activation and synergy with actin filaments during mitochondrial division

  2021cites this paper
• Mitochondrial dynamics and mitophagy in lung disorders.

  2021cites this paper
• Selective localization of Mfn2 near PINK1 enable its preferential ubiquitination by Parkin on mitochondria

  2021cites this paper
• Mitochondrial and Organellar Crosstalk in Parkinson’s Disease

  2021cites this paper
• A new functional role of mitochondria‐anchored protein ligase in peroxisome morphology in mammalian cells

  2021cites this paper
• ORP1L mediated PI(4)P signaling at ER-lysosome-mitochondrion three-way contact contributes to mitochondrial division

  2021cites this paper
• Inhibition of Mul1-mediated ubiquitination promotes mitochondria-associated translation

  2021cites this paper
• Therapeutic potential and recent advances on targeting mitochondrial dynamics in cardiac hypertrophy: A concise review

  2021cites this paper
• Understanding the Multiple Role of Mitochondria in Parkinson’s Disease and Related Disorders: Lesson From Genetics and Protein–Interaction Network

  2021cites this paper
• The cell biology of Parkinson’s disease

  2021cites this paper
• Protective Effects of Inhibition of Mitochondrial Fission on Organ Function After Sepsis

  2021cites this paper
• The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance

  2021cites this paper
• The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential

  2021cites this paper
• SUMO-specific Isopeptidases Tuning Cardiac SUMOylation in Health and Disease

  2021cites this paper
• Quality control of the mitochondrion.

  2021cites this paper
• Exogenous Alpha-Synuclein Evoked Parkin Downregulation Promotes Mitochondrial Dysfunction in Neuronal Cells. Implications for Parkinson’s Disease Pathology

  2021cites this paper
• Post-Translational Modification of Cysteines: A Key Determinant of Endoplasmic Reticulum-Mitochondria Contacts (MERCs)

  2021cites this paper
• The RING domain of mitochondrial E3 ubiquitin ligase 1 and its complex with Ube2D2: crystallization and X-ray diffraction.

  2020cites this paper
• Mitophagy in Alzheimer’s Disease and Other Age-Related Neurodegenerative Diseases

  2020cites this paper
• Mitochondrial Quality Control: Role in Cardiac Models of Lethal Ischemia-Reperfusion Injury

  2020cites this paper