Gene Symbol: dmfn
Description: Mitochondrial assembly regulatory factor
Alias: CG3869, CG38869, Dmel\CG3869, MARF, Marf-1, Mfn, Mfn-2, anon-WO0125274.3, dMFN, dMfn, dMfn2, dmfn, marf, mfn, mfn2, mitochondrial assembly regulatory factor, CG3869-PB, CG3869-PC, CG3869-PD, Marf-PB, Marf-PC, Marf-PD, drosophila mitofusin, mitochondria assembly regulatory factor, mitochondrial assembly, mitofusin, mitofusin/MARF, regulatory factor
Species: fruit fly

Top Publications

  1. Wu Z, Sawada T, Shiba K, Liu S, Kanao T, Takahashi R, et al. Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance. Genes Dev. 2013;27:157-62 pubmed publisher
    ..Genetically, mTORC2 and Trc act upstream of Parkin. Thus, multiplex kinase signaling is acting between PINK1 and Parkin to regulate MQC, a process highly conserved in mammals. ..
  2. Dorn G, Clark C, Eschenbacher W, Kang M, Engelhard J, Warner S, et al. MARF and Opa1 control mitochondrial and cardiac function in Drosophila. Circ Res. 2011;108:12-7 pubmed publisher
    ..melanogaster heart tubes with tinc?4Gal4-directed expression of RNA interference (RNAi) for mitochondrial assembly regulatory factor (MARF) and optic atrophy (Opa)1...
  3. Chen Y, Csordás G, Jowdy C, Schneider T, Csordás N, Wang W, et al. Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca(2+) crosstalk. Circ Res. 2012;111:863-75 pubmed publisher
    ..b>Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, whereas Mfn2 but not Mfn1 tethers endoplasmic ..
  4. Hwa J, Hiller M, Fuller M, Santel A. Differential expression of the Drosophila mitofusin genes fuzzy onions (fzo) and dmfn. Mech Dev. 2002;116:213-6 pubmed
    ..The fuzzy onions (fzo) and Drosophila mitofusin (dmfn) genes, which encode the only Mitofusin homologs in Drosophila are differentially expressed during ..
  5. Shiba Fukushima K, Inoshita T, Hattori N, Imai Y. PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila. PLoS Genet. 2014;10:e1004391 pubmed publisher
  6. Imai Y, Kanao T, Sawada T, Kobayashi Y, Moriwaki Y, Ishida Y, et al. The loss of PGAM5 suppresses the mitochondrial degeneration caused by inactivation of PINK1 in Drosophila. PLoS Genet. 2010;6:e1001229 pubmed publisher
    ..These results suggest that PGAM5 negatively regulates the PINK1 pathway related to maintenance of the mitochondria and, furthermore, that PGAM5 acts between PINK1 and Parkin, or functions independently of Parkin downstream of PINK1. ..
  7. Burman J, Yu S, Poole A, Decal R, Pallanck L. Analysis of neural subtypes reveals selective mitochondrial dysfunction in dopaminergic neurons from parkin mutants. Proc Natl Acad Sci U S A. 2012;109:10438-43 pubmed publisher
    ..Moreover, our neural purification method provides a foundation to further explore the pathogenesis of Parkinson disease, and to address other neurobiological questions requiring the analysis of defined neural cell types. ..
  8. Poole A, Thomas R, Yu S, Vincow E, Pallanck L. The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway. PLoS ONE. 2010;5:e10054 pubmed publisher
    ..We report that the steady-state abundance of the mitochondrial fusion-promoting factor Mitofusin (dMfn) is inversely correlated with the activity of PINK1 and Parkin in Drosophila...
  9. Park J, Lee G, Chung J. The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process. Biochem Biophys Res Commun. 2009;378:518-23 pubmed publisher
    ..the regulators of mitochondrial fusion and fission such as Drp1, which promotes mitochondrial fission, and Opa1 or Marf, which induces mitochondrial fusion...

More Information


  1. Ziviani E, Tao R, Whitworth A. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc Natl Acad Sci U S A. 2010;107:5018-23 pubmed publisher
    ..Furthermore, PINK1 and Parkin mediate the ubiquitination of the profusion factor Mfn on the outer surface of mitochondria...
  2. Liu S, Lu B. Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster. PLoS Genet. 2010;6:e1001237 pubmed publisher
    ..Our results reveal complex cellular responses to PINK1 inactivation and suggest novel therapeutic strategies through manipulation of the compensatory responses. ..
  3. Deng H, Dodson M, Huang H, Guo M. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A. 2008;105:14503-8 pubmed publisher maintained by a dynamic balance between the opposing actions of mitochondrial fusion, controlled by Mitofusin (mfn) and Optic atrophy 1 (opa1), and mitochondrial fission, controlled by drp1...
  4. Poole A, Thomas R, Andrews L, McBride H, Whitworth A, Pallanck L. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A. 2008;105:1638-43 pubmed publisher
    ..dosage and by heterozygous loss-of-function mutations affecting the mitochondrial fusion-promoting factors OPA1 and Mfn2. Finally, we find that an eye phenotype associated with increased PINK1/Parkin pathway activity is suppressed by ..
  5. Liu S, Sawada T, Lee S, Yu W, Silverio G, Alapatt P, et al. Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet. 2012;8:e1002537 pubmed publisher
    ..Moreover, the different effects of loss of PINK1 function on Miro protein level in Drosophila and mouse cells may offer one explanation of the distinct phenotypic manifestations of PINK1 mutants in these two species. ..
  6. Rana A, Rera M, Walker D. Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan. Proc Natl Acad Sci U S A. 2013;110:8638-43 pubmed publisher
    ..We show that the mitochondrial fusion-promoting factor Drosophila Mitofusin, a Parkin substrate, increases in abundance during aging...
  7. Schmidt I, Thomas S, Kain P, Risse B, Naffin E, Kl mbt C. Kinesin heavy chain function in Drosophila glial cells controls neuronal activity. J Neurosci. 2012;32:7466-76 pubmed publisher
    ..Our work shows that the role of Khc for neuronal excitability must be considered in the light of its necessity for directed transport in glia...
  8. Nagaraj R, Gururaja Rao S, Jones K, Slattery M, Negre N, Braas D, et al. Control of mitochondrial structure and function by the Yorkie/YAP oncogenic pathway. Genes Dev. 2012;26:2027-37 pubmed publisher
    ..up-regulation of genes that regulate mitochondrial fusion, such as opa1-like (opa1) and mitochondria assembly regulatory factor (Marf), and results in fused mitochondria with dramatic reduction in reactive oxygen species (ROS)..
  9. Debattisti V, Pendin D, Ziviani E, Daga A, Scorrano L. Reduction of endoplasmic reticulum stress attenuates the defects caused by Drosophila mitofusin depletion. J Cell Biol. 2014;204:303-12 pubmed publisher
    ..dysfunction ameliorates the functional and developmental defects of flies lacking the single Mfn mitochondrial assembly regulatory factor (Marf)...
  10. Yun J, Puri R, Yang H, Lizzio M, Wu C, Sheng Z, et al. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. elife. 2014;3:e01958 pubmed publisher
    ..The suppression is achieved through the ubiquitin-dependent degradation of Mitofusin, which itself causes PINK1/parkin mutant-like toxicity when overexpressed...
  11. Lee K, Wu Z, Song Y, Mitra S, Feroze A, Cheshier S, et al. Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway. Genes Dev. 2013;27:2642-7 pubmed publisher
    ..Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling. ..
  12. Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, et al. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015;160:177-90 pubmed publisher
  13. Gupte T. Mitochondrial Fragmentation Due to Inhibition of Fusion Increases Cyclin B through Mitochondrial Superoxide Radicals. PLoS ONE. 2015;10:e0126829 pubmed publisher
    ..Our results provide an insight into the need for mitofusin-degradation during mitosis and also help in understanding the mechanism by which mitofusins may function as ..
  14. Park J, Kim Y, Choi S, Koh H, Lee S, Kim J, et al. Drosophila Porin/VDAC affects mitochondrial morphology. PLoS ONE. 2010;5:e13151 pubmed publisher
    ..Collectively, our study showed that loss of Drosophila Porin results in mitochondrial morphological defects and suggested that the defective mitochondrial function by Porin deficiency affects the mitochondrial remodeling process. ..
  15. Bhandari P, Song M, Dorn G. Dissociation of mitochondrial from sarcoplasmic reticular stress in Drosophila cardiomyopathy induced by molecularly distinct mitochondrial fusion defects. J Mol Cell Cardiol. 2015;80:71-80 pubmed publisher three models of mitochondrial fragmentation in Drosophila cardiomyocytes: Drp1 expression, Opa1 RNAi, and mitofusin MARF RNA1...
  16. Shiba Fukushima K, Arano T, Matsumoto G, Inoshita T, Yoshida S, Ishihama Y, et al. Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering. PLoS Genet. 2014;10:e1004861 pubmed publisher
  17. Wang Z, Rabouille C, Geisbrecht E. Loss of a Clueless-dGRASP complex results in ER stress and blocks Integrin exit from the perinuclear endoplasmic reticulum in Drosophila larval muscle. Biol Open. 2015;4:636-48 pubmed publisher
    ..This, in turn, is essential for integrin subunit αPS2 ER exit in Drosophila larval myofibers. ..
  18. Hwang R, Wiemerslage L, LaBreck C, Khan M, Kannan K, Wang X, et al. The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson's disease. Neurobiol Dis. 2014;69:180-91 pubmed publisher
  19. Deng Q, Guo T, Zhou X, Xi Y, Yang X, Ge W. Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development. Genetics. 2016;203:1777-88 pubmed publisher
    ..In addition, depletion of other mitochondrial fusion components, Opa1 or Marf, inactivates the Hippo pathway as well...
  20. Celardo I, Costa A, Lehmann S, Jones C, Wood N, Mencacci N, et al. Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson's disease. Cell Death Dis. 2016;7:e2271 pubmed publisher
    ..We show that enhanced ER stress signalling in pink1 and parkin mutants is mediated by mitofusin bridges, which occur between defective mitochondria and the ER...
  21. Fergestad T, Bostwick B, Ganetzky B. Metabolic disruption in Drosophila bang-sensitive seizure mutants. Genetics. 2006;173:1357-64 pubmed
    ..Our data implicate cellular metabolism in regulating seizure susceptibility and suggest that differential sensitivity of neuronal subtypes to metabolic changes underlies distinct types of seizure activity. ..
  22. Rai M, Nongthomba U. Effect of myonuclear number and mitochondrial fusion on Drosophila indirect flight muscle organization and size. Exp Cell Res. 2013;319:2566-77 pubmed publisher
    ..Our results establish the organization levels of DLMs and highlight the importance of the appropriate number of nuclei and mitochondrial fusion in determining the overall organization, growth and size of DLMs. ..
  23. López Del Amo V, Seco Cervera M, García Giménez J, Whitworth A, Pallardó F, Galindo M. Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy. Hum Mol Genet. 2015;24:21-36 pubmed publisher
  24. Banerjee S, Chinthapalli B. A proteomic screen with Drosophila Opa1-like identifies Hsc70-5/Mortalin as a regulator of mitochondrial morphology and cellular homeostasis. Int J Biochem Cell Biol. 2014;54:36-48 pubmed publisher
    ..influences mitochondrial morphology through interaction with 'mitochondria-shaping' proteins like Mitochondrial assembly regulatory factor (Marf) and Drosophila Mitofilin (dMitofilin)...
  25. Hao L, Giasson B, Bonini N. DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function. Proc Natl Acad Sci U S A. 2010;107:9747-52 pubmed publisher
    ..These findings link DJ-1, pink1, and parkin to mitochondrial integrity and provide the foundation for therapeutics that link bioenergetics and parkinsonism. ..
  26. Mitra K, Rikhy R, Lilly M, Lippincott Schwartz J. DRP1-dependent mitochondrial fission initiates follicle cell differentiation during Drosophila oogenesis. J Cell Biol. 2012;197:487-97 pubmed publisher
    ..Reintroduction of mitochondrial fission activity or inhibition of the mitochondrial fusion protein Marf-1 in posterior-localized DRP1-null clones reversed the block in Notch-dependent differentiation...
  27. DUBOFF B, Götz J, Feany M. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron. 2012;75:618-32 pubmed publisher
    ..Our results thus identify actin-mediated disruption of mitochondrial dynamics as a direct mechanism of tau toxicity in neurons in vivo...
  28. Bhandari P, Song M, Chen Y, Burelle Y, Dorn G. Mitochondrial contagion induced by Parkin deficiency in Drosophila hearts and its containment by suppressing mitofusin. Circ Res. 2014;114:257-65 pubmed publisher
    ..Limiting mitochondrial contagion by inhibiting organelle fusion shows promise for minimizing organ dysfunction produced by defective mitophagic signaling...
  29. Li Y, Hassinger L, Thomson T, Ding B, Ashley J, Hassinger W, et al. Lamin Mutations Accelerate Aging via Defective Export of Mitochondrial mRNAs through Nuclear Envelope Budding. Curr Biol. 2016;26:2052-2059 pubmed publisher
    ..We identified mitochondrial assembly regulatory factor (Marf), a mitochondrial fusion factor (mitofusin), as well as other transcripts required for ..
  30. Rival T, Macchi M, Arnauné Pelloquin L, Poidevin M, Maillet F, Richard F, et al. Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways. EMBO Rep. 2011;12:223-30 pubmed publisher
    ..epistatic experiments indicate that PMI shapes the mitochondria through a mechanism that is independent of drp1 and mfn. This shows that mitochondrial networks can be shaped in higher eukaryotes by at least two separate pathways: one ..
  31. Khalil B, El Fissi N, Aouane A, Cabirol Pol M, Rival T, Liévens J. PINK1-induced mitophagy promotes neuroprotection in Huntington's disease. Cell Death Dis. 2015;6:e1617 pubmed publisher
    ..This neuroprotection was Parkin-dependent and required mitochondrial outer membrane proteins, mitofusin and the voltage-dependent anion channel...
  32. Kim N, Tresse E, Kolaitis R, Molliex A, Thomas R, Alami N, et al. VCP is essential for mitochondrial quality control by PINK1/Parkin and this function is impaired by VCP mutations. Neuron. 2013;78:65-80 pubmed publisher
    ..Further, VCP and its adaptor Npl4/Ufd1 are required for clearance of damaged mitochondria via the PINK1/Parkin pathway, and this is impaired by pathogenic mutations in VCP. ..
  33. Burchell V, Nelson D, Sanchez Martinez A, Delgado Camprubi M, Ivatt R, Pogson J, et al. The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci. 2013;16:1257-65 pubmed publisher
    ..with reduced Fbxo7 expression showed deficiencies in translocation of Parkin to mitochondria, ubiquitination of mitofusin 1 and mitophagy...
  34. Ratnaparkhi A. Signaling by Folded gastrulation is modulated by mitochondrial fusion and fission. J Cell Sci. 2013;126:5369-76 pubmed publisher
    ..The findings presented here show that mitochondria, through regulation of fusion and fission, function as downstream effectors and modulators of Fog signaling and Fog-dependent cell shape change. ..
  35. Oliveira D, Almeida F, O Grady P, Armella M, DeSalle R, Etges W. Monophyly, divergence times, and evolution of host plant use inferred from a revised phylogeny of the Drosophila repleta species group. Mol Phylogenet Evol. 2012;64:533-44 pubmed publisher
    ..Concordant with our proposed timing of host use shifts, these dates are consistent with the suggested times when the Opuntioideae originated in South America. We discuss the generally accepted South American origin of the repleta group. ..
  36. Sandoval H, Yao C, Chen K, Jaiswal M, Donti T, Lin Y, et al. Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production. elife. 2014;3: pubmed publisher
    ..We show that Marf (Mitochondrial associated regulatory factor), is required for mitochondrial fusion and transport in long axons...
  37. Senyilmaz D, Virtue S, Xu X, Tan C, Griffin J, Miller A, et al. Regulation of mitochondrial morphology and function by stearoylation of TFR1. Nature. 2015;525:124-8 pubmed publisher
    ..This leads to reduced ubiquitination of mitofusin via HUWE1, thereby promoting mitochondrial fusion and function...
  38. Khalil B, Cabirol Pol M, Miguel L, Whitworth A, Lecourtois M, Liévens J. Enhancing Mitofusin/Marf ameliorates neuromuscular dysfunction in Drosophila models of TDP-43 proteinopathies. Neurobiol Aging. 2017;54:71-83 pubmed publisher correlated with a specific decrease in the mRNA and protein levels of the Drosophila profusion gene mitofusin/marf...
  39. Eschenbacher W, Song M, Chen Y, Bhandari P, Zhao P, Jowdy C, et al. Two rare human mitofusin 2 mutations alter mitochondrial dynamics and induce retinal and cardiac pathology in Drosophila. PLoS ONE. 2012;7:e44296 pubmed publisher
    ..Inexplicably, loss of function mutations of mitofusin 2 (Mfn2) specifically affect neurological tissue, causing Charcot Marie Tooth syndrome (CMT) and atypical optic ..
  40. Zhang Y, Liu X, Bai J, Tian X, Zhao X, Liu W, et al. Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis. Mol Cell. 2016;61:111-24 pubmed publisher
    ..MIGA proteins function downstream of mitofusin and interact with MitoPLD to stabilize MitoPLD and facilitate MitoPLD dimer formation...
  41. Wang Z, Clark C, Geisbrecht E. Drosophila clueless is involved in Parkin-dependent mitophagy by promoting VCP-mediated Marf degradation. Hum Mol Genet. 2016;25:1946-1964 pubmed
    PINK1/Parkin-mediated mitochondrial quality control (MQC) requires valosin-containing protein (VCP)-dependent Mitofusin/Marf degradation to prevent damaged organelles from fusing with the healthy mitochondrial pool, facilitating ..
  42. Lee S, Lee K, Huh S, Liu S, Lee D, Hong S, et al. Polo Kinase Phosphorylates Miro to Control ER-Mitochondria Contact Sites and Mitochondrial Ca(2+) Homeostasis in Neural Stem Cell Development. Dev Cell. 2016;37:174-189 pubmed publisher
    ..Our results elucidate a regulatory mechanism underlying Ca²? mito homeostasis and how its dysregulation may affect NSC metabolism/development and contribute to disease. ..
  43. Thomenius M, Freel C, Horn S, Krieser R, Abdelwahid E, Cannon R, et al. Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death. Cell Death Differ. 2011;18:1640-50 pubmed publisher
    ..mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf...
  44. Thomas R, Andrews L, Burman J, Lin W, Pallanck L. PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the mitochondrial matrix. PLoS Genet. 2014;10:e1004279 pubmed publisher
    ..Our findings thus suggest that Lon plays an essential role in regulating the PINK1-Parkin pathway by promoting the degradation of PINK1 in the matrix of healthy mitochondria. ..