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

Braschi, Emélie; Zunino, Rodolfo; McBride, Heidi M.

doi:10.1038/embor.2009.86

Cited by 307 publications

(289 citation statements)

References 25 publications

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“…All three members of the Arabidopsis SP1 protein family share limited sequence similarities with the human MAPL (mitochondrial-anchored protein ligase) protein, a regulator of mitochondrial fission that targets the dynamin-related protein DRP1 (56). Neither SP1 nor MAPL has obviously similar sequences in yeast or nematode, suggesting that this family of E3 enzymes may be present only in higher eukaryotes.…”

Section: Discussionmentioning

confidence: 99%

E3 ubiquitin ligase SP1 regulates peroxisome biogenesis in Arabidopsis

Pan

Satkovich

2016

Proc. Natl. Acad. Sci. U.S.A.

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Peroxisomes are ubiquitous eukaryotic organelles that play pivotal roles in a suite of metabolic processes and often act coordinately with other organelles, such as chloroplasts and mitochondria. Peroxisomes import proteins to the peroxisome matrix by peroxins (PEX proteins), but how the function of the PEX proteins is regulated is poorly understood. In this study, we identified the Arabidopsis RING (really interesting new gene) type E3 ubiquitin ligase SP1 [suppressor of plastid protein import locus 1 (ppi1) 1] as a peroxisome membrane protein with a regulatory role in peroxisome protein import. SP1 interacts physically with the two components of the peroxisome protein docking complex PEX13-PEX14 and the (RING)-finger peroxin PEX2. Loss of SP1 function suppresses defects of the pex14-2 and pex13-1 mutants, and SP1 is involved in the degradation of PEX13 and possibly PEX14 and all three RING peroxins. An in vivo ubiquitination assay showed that SP1 has the ability to promote PEX13 ubiquitination. Our study has revealed that, in addition to its previously reported function in chloroplast biogenesis, SP1 plays a role in peroxisome biogenesis. The same E3 ubiquitin ligase promotes the destabilization of components of two distinct protein-import machineries, indicating that degradation of organelle biogenesis factors by the ubiquitin-proteasome system may constitute an important regulatory mechanism in coordinating the biogenesis of metabolically linked organelles in eukaryotes.peroxisome biogenesis | E3 ubiquitin ligase | protein import | peroxin | SP1

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Section: Discussionmentioning

confidence: 99%

E3 ubiquitin ligase SP1 regulates peroxisome biogenesis in Arabidopsis

Pan

Satkovich

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The middle domain has been implicated in the oligomerization of DLP1 required for its membrane-constricting properties (22), and the CC domain interacts with the N-terminal domains to regulate the GTPase activity. These domains of the protein are the subject of multiple posttranslational modifications, including phosphorylation (21,31,61,132,151), S-nitrosylation (25), SUMOylation (11,51,62,139), and ubiquitylation (94,144), affecting DLP1 function, interactions, stability, and subcellular localization.…”

Section: The Core Machinery For Mitochondrial Fission and Fusionmentioning

confidence: 99%

Mitochondrial Morphology in Metabolic Diseases

Galloway

Yoon

2013

Antioxidants & Redox Signaling

116

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Significance: Mitochondria are the cellular energy-producing organelles and are at the crossroad of determining cell life and death. As such, the function of mitochondria has been intensely studied in metabolic disorders, including diabetes and associated maladies commonly grouped under all-inclusive pathological condition of metabolic syndrome. More recently, the altered metabolic profiles and function of mitochondria in these ailments have been correlated with their aberrant morphologies. This review describes an overview of mitochondrial fission and fusion machineries, and discusses implications of mitochondrial morphology and function in these metabolic maladies. Recent Advances: Mitochondria undergo frequent morphological changes, altering the mitochondrial network organization in response to environmental cues, termed mitochondrial dynamics. Mitochondrial fission and fusion mediate morphological plasticity of mitochondria and are controlled by membrane-remodeling mechanochemical enzymes and accessory proteins. Growing evidence suggests that mitochondrial dynamics play an important role in diabetes establishment and progression as well as associated ailments, including, but not limited to, metabolism-secretion coupling in the pancreas, nonalcoholic fatty liver disease progression, and diabetic cardiomyopathy. Critical Issues: While mitochondrial dynamics are intimately associated with mitochondrial bioenergetics, their cause-and-effect correlation remains undefined in metabolic diseases. Future Directions: The involvement of mitochondrial dynamics in metabolic diseases is in its relatively early stages. Elucidating the role of mitochondrial dynamics in pathological metabolic conditions will aid in defining the intricate form-function correlation of mitochondria in metabolic pathologies and should provide not only important clues to metabolic disease progression, but also new therapeutic targets. Antioxid. Redox Signal. 19,[415][416][417][418][419][420][421][422][423][424][425][426][427][428][429][430]

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“…The fact that a mitochondrial protein could be a SUMO substrate has been investigated lately, and very recently a specific E3 ligase catalyzing specific SUMO conjugation to mitochondrial targets has been identified (4).…”

Section: Fig 5 Validation Of Metacaspase-3 As a Sumoylation Targetmentioning

confidence: 99%

“…In yeast and mammalian cells a prominent role for SUMO in several important cellular processes, such as DNA replication and repair, chromosome segregation, gene expression, and nuclear trafficking was described (4,5). Moreover, results from large-scale proteomic studies provided a great number of potential SUMO targets, suggesting that a broader spectrum of biological processes could be influenced by this posttranslational modification (6 -17).…”

mentioning

confidence: 99%

SUMOylation Pathway in Trypanosoma cruzi: Functional Characterization and Proteomic Analysis of Target Proteins

Bayona

Nakayasu

Laverrière

et al. 2011

Molecular & Cellular Proteomics

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SUMOylation is a relevant protein post-translational modification in eukaryotes. The C terminus of proteolytically activated small ubiquitin-like modifier (SUMO) is covalently linked to a lysine residue of the target protein by an isopeptide bond, through a mechanism that includes an E1-activating enzyme, an E2-conjugating enzyme, and transfer to the target, sometimes with the assistance of a ligase. The modification is reversed by a protease, also responsible for SUMO maturation. A number of proteins have been identified as SUMO targets, participating in the regulation of cell cycle progression, transcription, translation, ubiquitination, and DNA repair. In this study, we report that orthologous genes corresponding to the SUMOylation pathway are present in the etiological agent of Chagas disease, Trypanosoma cruzi. Furthermore, the SUMOylation system is functionally active in this protozoan parasite, having the requirements for SUMO maturation and conjugation. Immunofluorescence analysis showed that T. cruzi SUMO (TcSUMO) is predominantly found in the nucleus. To identify SUMOylation targets and get an insight into their physiological roles we generated transfectant T. cruzi epimastigote lines expressing a double-tagged T. cruzi SUMO, and SUMOylated proteins were enriched by tandem affinity chromatography. By two-dimensional liquid chromatography-mass spectrometry a total of 236 proteins with diverse biological functions were identified as potential T. cruzi SUMO targets. Of these, metacaspase-3 was biochemically validated as a bona fide SUMOylation substrate. Proteomic studies in other organisms have reported that orthologs of putative T.

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

Cited by 307 publications

References 25 publications

E3 ubiquitin ligase SP1 regulates peroxisome biogenesis in Arabidopsis

E3 ubiquitin ligase SP1 regulates peroxisome biogenesis in Arabidopsis

Mitochondrial Morphology in Metabolic Diseases

SUMOylation Pathway in Trypanosoma cruzi: Functional Characterization and Proteomic Analysis of Target Proteins

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