Mitochondrial dynamics protein MID49

MIEF2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4WOY
Identifiers
Aliases	MIEF2, SMCR7, mitochondrial elongation factor 2, MID49, COXPD49
External IDs	OMIM: 615498 MGI: 2144199 HomoloGene: 27354 GeneCards: MIEF2
Gene location (Human) Chr. Chromosome 17 (human) Band 17p11.2 Start 18,260,597 bp End 18,266,552 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 B2 Start 60,619,224 bp End 60,623,777 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle left ventricle skeletal muscle tissue prefrontal cortex kidney left adrenal gland right adrenal gland right uterine tube salivary gland minor salivary glands Top expressed in knee joint skeletal muscle tissue quadriceps femoris muscle gastrocnemius muscle tibialis anterior muscle ankle temporal muscle sternocleidomastoid muscle vastus lateralis muscle triceps brachii muscle More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding identical protein binding Cellular component integral component of membrane mitochondrial outer membrane peroxisome membrane mitochondrion Biological process mitochondrial fusion positive regulation of protein homooligomerization mitochondrion organization positive regulation of mitochondrial fission positive regulation of protein targeting to membrane regulation of mitochondrion organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 125170 237781 Ensembl ENSG00000284495 ENSG00000177427 ENSMUSG00000018599 UniProt Q96C03 Q5NCS9 RefSeq (mRNA) NM_148886 NM_001144900 NM_139162 NM_001009927 RefSeq (protein) NP_001138372 NP_631901 NP_683684 NP_001009927 Location (UCSC) Chr 17: 18.26 – 18.27 Mb Chr 11: 60.62 – 60.62 Mb PubMed search
Wikidata
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Mitochondrial elongation factor 2 is a protein that in humans is encoded by the MIEF2 gene.

MID49 Protein Structure

The MID49 protein is used to assist in mitochondrial binary fission. It is a dynamic peripheral protein receptor found on the surface of the mitochondrial membrane. MID51 is a very similar protein and studies have shown that it has a variant nucleotidyl transferase structure which allows it to move phosphates as a co-factor. This structure and ability is essential because it allows it to interact with ADP which will activate the Drp1 protein. Further studies have shown that MID49 and MID51 are homologous in sequence and MID49 also has a nucleotidyl transferase domain but it is still unknown if MID49 can also bind a co-factor. Instead of a co-factor ligand, it was found that MID49 has a loop structure on its surface that allows it to physically interact with the Drp1 protein. To recap, the MID51 and MID49 are both similar proteins that recruit Drp1 protein to induce mitochondrial binary fission but they have small differences in structure which allows them to bind Drp1 in different ways.

MID49 Protein's Role in Mitochondrial Binary Fission

The MID49 peripheral protein will attract the Drp1 to the surface of the mitochondrial membrane which then induces endoplasmic reticulum contact. The ER then releases Ca2+ into the mitochondria once there is physical contact at the membrane. The influx of calcium induces a constriction response in the mitochondria. With this constriction in the middle, the MID49 keeps recruiting more and more Drp1 proteins to make a sort of chain structure to wrap around that narrowed area called the oligomeric ring. The Drp1 proteins will eventually disassociate with the MID49 proteins through hydrolysis which causes a much tighter constriction around the mitochondria. There are still studies being done to confirm if this constriction alone will then split the mitochondria in the middle to complete a binary fission event.

Function

This gene encodes an outer mitochondrial membrane protein that functions in the regulation of mitochondrial morphology. It can directly recruit the fission mediator dynamin-related protein 1 (Drp1) to the mitochondrial surface. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011].

References

(Updated 2 and 3 reference list)

2. Losón, Oliver C; Meng, Shuxia; Ngo, Huu; Liu, Raymond; Kaiser, Jens T; Chan, David C (2015–3). "Crystal structure and functional analysis of MiD49, a receptor for the mitochondrial fission protein Drp1". Protein Science.

3. Fenton, Adam R.; Jongens, Thomas A.; Holzbaur, Erika L. F. (2021-02-01). "Mitochondrial dynamics: Shaping and remodeling an organelle network". Current Opinion in Cell Biology. Cell Architecture. 68: 28–36.

Further reading

• Sarimski K (2004). "Communicative competence and behavioural phenotype in children with Smith-Magenis syndrome". Genet. Couns. 15 (3): 347–55. PMID 15517828.
• Palmer CS, Osellame LD, Laine D, Koutsopoulos OS, Frazier AE, Ryan MT (June 2011). "MiD49 and MiD51, new components of the mitochondrial fission machinery". EMBO Rep. 12 (6): 565–73. doi:10.1038/embor.2011.54. PMC 3128275. PMID 21508961.
• Palmer CS, Osellame LD, Laine D, Koutsopoulos OS, Frazier AE, Ryan MT (June 2011). "MiD49 and MiD51, new components of the mitochondrial fission machinery". EMBO Rep. 12 (6): 565–73. doi:10.1038/embor.2011.54. PMC 3128275. PMID 21508961.
• Losón OC, Song Z, Chen H, Chan DC (March 2013). "Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission". Mol. Biol. Cell. 24 (5): 659–67. doi:10.1091/mbc.E12-10-0721. PMC 3583668. PMID 23283981.
• Liu T, Yu R, Jin SB, Han L, Lendahl U, Zhao J, Nistér M (November 2013). "The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics". Exp. Cell Res. 319 (18): 2893–904. doi:10.1016/j.yexcr.2013.07.010. PMID 23880462.
• Palmer CS, Elgass KD, Parton RG, Osellame LD, Stojanovski D, Ryan MT (September 2013). "Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission". J. Biol. Chem. 288 (38): 27584–93. doi:10.1074/jbc.M113.479873. PMC 3779755. PMID 23921378.
• Xu S, Cherok E, Das S, Li S, Roelofs BA, Ge SX, Polster BM, Boyman L, Lederer WJ, Wang C, Karbowski M (January 2016). "Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein". Mol. Biol. Cell. 27 (2): 349–59. doi:10.1091/mbc.E15-09-0678. PMC 4713136. PMID 26564796.
• Otera H, Miyata N, Kuge O, Mihara K (February 2016). "Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling". J. Cell Biol. 212 (5): 531–44. doi:10.1083/jcb.201508099. PMC 4772499. PMID 26903540.
• Atkins K, Dasgupta A, Chen KH, Mewburn J, Archer SL (November 2016). "The role of Drp1 adaptor proteins MiD49 and MiD51 in mitochondrial fission: implications for human disease". Clin. Sci. 130 (21): 1861–74. doi:10.1042/CS20160030. PMID 27660309.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.