ライフサイエンスコーパス: mitofusin

1 tors, and the mitochondrial fusion proteins (mitofusins).

2 active alleles with respect to regulation of Mitofusin.

3 physin and mitofusin; and 4) calcineurin and mitofusin.

4 s, which is mediated by large GTPases called mitofusins.

5 ructure required reactive oxygen species and mitofusins.

6 l homology between Drosophila MARF and human mitofusins.

7 f mitochondria, likely by the elimination of mitofusins.

8 Fusion of the outer membranes requires mitofusins.

9 e function and involves large GTPases called mitofusins.

10 Mitofusin 1 (Mfn1) or dominant-negative Dynamin related

11 rp neurons by cell-selectively knocking down mitofusin 1 (Mfn1) or mitofusin 2 (Mfn2) resulted in alt

12 es protein ubiquitination and degradation of mitofusin 1 (Mfn1), a molecule required for maintaining

13 alcium oscillations/contractile activity and mitofusin 1 (Mfn1), because (i) verapamil suppressed bot

14 ane fusion by investigating the structure of mitofusin 1 (MFN1).

15 of several mitochondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of

16 of Parkin to mitochondria, ubiquitination of mitofusin 1 and mitophagy.

17 nection, and was suppressed in cells lacking mitofusin 1 and optic atrophy 1 (OPA1), the key proteins

18 Conversely, a marked reduction in mitofusin 1 expression, which plays an essential role in

19 cells with the mitochondrial fusion proteins mitofusin 1 or 2 or with Drp1(K38A), a dominant-negative

20 sion of the mitochondrial fusion genes Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optic atrophy 1)

21 -related protein 1), Fis1 (fission 1), Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optric atrophy 1

22 tion in the expression of the fusion protein mitofusin 1.

23 tion of a validated mitochondrial substrate, mitofusin 1.

24 king the GTPases responsible for OMM fusion, mitofusins 1 and 2 (MFN1 and MFN2), display more heterog

25 sion required the action of fusion mediators mitofusins 1 and 2.

26 lated protein-1, 47%) and the fusion protein mitofusin-1 (35%) but not mitofusin-2.

27 Mitofusin-2 rescues the loss of LD but both Mitofusin-1 and Mitofusin-2 are required for steroid-hor

28 Previous studies have shown that mitofusin 2 (Mfn-2) (or hyperplasia suppressor gene [HSG

29 eract with the mitochondrial fusion mediator mitofusin 2 (Mfn2) and that may participate in mitochond

30 utations in the mitochondrial fusion protein mitofusin 2 (MFN2) are the most commonly identified caus

31 o-expression of mitochondrial fusion protein mitofusin 2 (Mfn2) could abolish TDP-43 induced mitochon

32 Mice lacking mitofusin 2 (Mfn2) in hearts have impaired parkin-mediat

33 The outer mitochondrial membrane GTPase mitofusin 2 (Mfn2) is known to regulate endoplasmic reti

34 In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion

35 ectively knocking down mitofusin 1 (Mfn1) or mitofusin 2 (Mfn2) resulted in altered mitochondria size

36 mination of the mitochondrial fusion protein mitofusin 2 (Mfn2) sensitizes PT cells to apoptosis in v

37 Mitofusin 2 (Mfn2), a membrane protein implicated in ER-

38 xonopathy in CMT2A is caused by mutations in Mitofusin 2 (Mfn2), a mitochondrial GTPase necessary for

39 Mitofusin 2 (Mfn2), a mitochondrial protein, was shown t

40 critical regulator of HSCs, Prdm16, induces mitofusin 2 (Mfn2), a protein involved in mitochondrial

41 Among them, in mammalian cells, mitofusin 2 (Mfn2), located on both the outer mitochondr

42 Cells lacking mitofusin 2 (Mfn2), which exhibit similar fusion defects

43 we identified a unique mutation in the gene mitofusin 2 (MFN2).

44 t rs1474868 coincides with the eQTL peak for mitofusin 2 (MFN2).

45 ress, serum deprivation or reduced levels of mitofusin 2 (MFN2).

46 hip between the conformational plasticity of mitofusin 2 and mitochondrial dynamism reveals a central

47 nt optic atrophy, are caused by mutations in mitofusin 2 and OPA1, suggesting that proper regulation

48 Mutations in Mitofusin 2 have been found to cause dominant forms of C

49 JNK phosphorylation of mitofusin 2 in response to cellular stress leads to recr

50 The stability of a nonphosphorylatable mitofusin 2 mutant is unaffected by stress and protectiv

51 Conversely, a mitofusin 2 phosphomimic is more rapidly degraded withou

52 ted form of the mitochondrial fusion protein Mitofusin 2 serves as a receptor for Parkin translocatio

53 Genetic mutations in MFN2 (the gene encoding mitofusin 2) interrupt mitochondrial fusion and cause th

54 Mfn2 (mitofusin 2), a mitochondrial membrane protein that part

55 drial fusion genes Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optic atrophy 1) and Tomm40.

56 Fis1 (fission 1), Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optric atrophy 1), Tomm40 (transloca

57 MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial

58 biquitin-mediated proteasomal degradation of mitofusin 2, leading to mitochondrial fragmentation and

59 hondrial proteins, including mitofusin 1 and mitofusin 2, were detected within 3 h of CCCP treatment.

60 link between stress-induced JNK activation, mitofusin 2, which is an essential component of the mito

61 Huwe1/Mule/ARF-BP1/HectH9/E3Histone/Lasu1 to mitofusin 2, with the BH3 domain of Huwe1 implicated in

62 The effects of adenoviral mitofusin-2 (Ad-MFN2) overexpression were measured in vi

63 Mitofusin-2 (Mfn-2) is a dynamin-like protein that is in

64 in the outer mitochondrial membrane, notably mitofusin-2 (Mfn-2), which promotes fusion, and dynamin-

65 RP-1) pharmacologically or by overexpressing mitofusin-2 (Mfn-2).

66 contribution of decreased fusion and reduced mitofusin-2 (MFN2) expression to PAH is unknown.

67 The mitochondrial GTPase mitofusin-2 (MFN2) has previously been reported to play

68 However, C-cleavage requires Mitofusin-2 (Mfn2), a key factor in mitochondria-ER teth

69 Mitofusin-2 and calcineurin were positively correlated i

70 cues the loss of LD but both Mitofusin-1 and Mitofusin-2 are required for steroid-hormone synthesis.

71 ligase for this chain type, and we show that mitofusin-2 is modified with K6-linked polyubiquitin in

72 Interestingly, human Mitofusin-2 rescues the loss of LD but both Mitofusin-1

73 Protein levels of synaptophysin, mitofusin-2, vGLUT1, and calcineurin did not differ betw

74 tative kinase 1 expression and the dependent mitofusin-2-Parkin interaction.

75 the fusion protein mitofusin-1 (35%) but not mitofusin-2.

76 chondrial fusion-promoting factor Drosophila Mitofusin, a Parkin substrate, increases in abundance du

77 Here we show that mitofusins adopt either a fusion-constrained or a fusion

78 We show that mitofusin, an integral mitochondrial membrane protein, i

79 Decreased levels of mitofusin and increased levels of ATPIF1, an inhibitor o

80 via PINK1 action and can ubiquitylate porin, mitofusin and Miro proteins on the MOM, the full reperto

81 ilize the fusion-constrained conformation of mitofusin and promote the fusion-permissive conformation

82 These studies indicate that mitofusins and OPA1 are essential for mitochondrial fusi

83 These results indicate that mammalian mitofusins and OPA1 mediate distinct sequential fusion s

84 ive stress and are reciprocally regulated by mitofusins and Parkin.

85 c oxidase and its tyrosine phosphorylation, mitofusins and PGC-1alpha.

86 known inter-mitochondrial tethering proteins mitofusins and rapidly induced by the stable rapprocheme

87 In addition, unlike mitofusins and yeast Mgm1, OPA1 is not required on adjac

88 tress-induced fusion requires PINK1 (PARK6), mitofusins, and parkin ubiquitin ligase activity.

89 physin and calcineurin; 3) synaptophysin and mitofusin; and 4) calcineurin and mitofusin.

90 Mitofusins are conserved GTPases essential for the fusio

91 Mitofusins are dynamin-related GTPases that are essentia

92 actor (Marf), a mitochondrial fusion factor (mitofusin), as well as other transcripts required for mi

93 bility and causes degeneration via enhancing mitofusin-associated mitochondrial fusion, which provide

94 Downregulation of the mitofusins by shRNA to ~45% or ~52% of the control level

95 Loss of the mitofusins causes severe mitochondrial dysfunction, comp

96 dria to mediate fusion, which indicates that mitofusin complexes act in trans (that is, between adjac

97 cted transmembrane domains, whereas metazoan Mitofusins contain only a single transmembrane domain.

98 ed these mitochondrial dynamics by promoting mitofusin degradation.

99 These findings unravel key features of mitofusin-dependent fusion of outer membranes and consti

100 r binding interactions, and demonstrate that mitofusin-dependent mitochondrial fusion can be regulate

101 s study was to determine the significance of mitofusins during early postnatal cardiac development.

102 ng the mitochondrial fusion-promoting factor mitofusin for degradation through an endoplasmic reticul

103 ion, in part because the structural basis of mitofusin function is not completely understood.

104 teracts Mdm30-mediated turnover of the yeast mitofusin Fzo1 and that Mdm30 targets Ubp2 for degradati

105 We used the conserved yeast mitofusin FZO1 to study the molecular consequences of CM

106 dress this issue, we have analyzed the yeast mitofusin Fzo1p and find that mutation of any of the thr

107 Mfn2 is one of two mammalian mitofusin GTPases that promote mitochondrial fusion and

108 Deficiency in mitofusins impaired the electric activity of Agrp neuron

109 These experiments identify a role for mitofusins in directly regulating mitochondrial transpor

110 exes and the close interplay between the two mitofusins in the control of mitochondrial fusion.

111 d a fundamental role for the dynamin-related mitofusins in the tethering mechanism, thereby ensuring

112 ired for proteasome-dependent degradation of Mitofusins in vitro and in vivo.

113 Consistent with this proposal, truncated mitofusin, in an HR2-dependent manner, causes mitochondr

114 Gp78 in HT-1080 fibrosarcoma cells increased mitofusin levels and reduced depolarization-induced mito

115 overexpression results in reduced Drosophila Mitofusin levels in aging flies, with concomitant change

116 s valosin-containing protein (VCP)-dependent Mitofusin/Marf degradation to prevent damaged organelles

117 findings from in vivo mouse models in which mitofusin-mediated mitochondrial fusion or dynamin-relat

118 Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer memb

119 iology often relied upon the exploitation of Mitofusin (Mfn) 2 as an ER-mitochondria tether.

120 rial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged

121 A mitofusin (Mfn) 2 mutant lacking PINK1 phosphorylation s

122 tions of mitochondrial fusion, controlled by Mitofusin (mfn) and Optic atrophy 1 (opa1), and mitochon

123 ein expression or that of its central target mitofusin (Mfn) in the absence of HSP72.

124 and proteasome-dependent degradation of the mitofusin (Mfn) mitochondrial fusion factors Mfn1/Mfn2.

125 nction or a contributor to the phenotypes in mitofusin (Mfn)-depleted Drosophila melanogaster is uncl

126 ct, as it is mediated instead by the protein Mitofusin (Mfn).

127 Cardiomyocyte expression of human mitofusin (mfn)1 or -2 rescued MARF RNAi cardiomyopathy,

128 The murine mfn1 and mfn2 genes, encoding mitofusins (Mfn) 1 and 2 that mediate mitochondrial teth

129 Mitofusins (Mfn-1 and Mfn-2) are known regulators of mit

130 Because the mitofusins Mfn1 and Mfn2 are essential for mitochondrial

131 Although the mitofusins Mfn1 and Mfn2 are rapid degradation targets o

132 Here we show that ubiquitination of mitofusins Mfn1 and Mfn2, large GTPases that mediate mit

133 l muscle through conditional deletion of the mitofusins Mfn1 and Mfn2, mitochondrial GTPases essentia

134 Three large GTPases--OPA1 and the mitofusins Mfn1 and Mfn2--are essential for the fusion o

135 Mitofusins (Mfn1 and Mfn2) are outer mitochondrial membr

136 Despite the established role of mitofusins (MFN1 and MFN2) in mitochondrial fusion, only

137 ncreased fusion proteins, including OPA1 and mitofusins (Mfn1, Mfn2) and reduced the ubiquitination o

138 n acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 (Drp1

139 The mitofusins, Mfn1 and Mfn2, have been shown to affect mit

140 with known mediators of mitochondrial fusion-mitofusins (Mfns) 1 and 2-and enhances the GTP-binding c

141 uitin ligase that induces degradation of the mitofusin mitochondrial fusion proteins and mitochondria

142 It is not known how mitofusin mutations cause axonal degeneration and CMT2A

143 A heptad repeat region (HR2) mediates mitofusin oligomerization by assembling a dimeric, antip

144 ry, including the dynamin-like GTPases Drp1, Mitofusin, Opa1, and the Drp1-interacting protein Fis1,

145 er cells, as driven by downregulation of the mitofusin protein MFN2, leading to reduced oxidative pho

146 uctions revealed that fungal Fzo1 and animal Mitofusin proteins are highly diverged from one another

147 Furthermore, the expression of Opa-1 and mitofusins, proteins of the mitochondrial fusion machine

148 molecular basis of mitochondrial fusion and mitofusin-related human neuromuscular disorders.

149 PINK1/parkin pathway or decreased levels of mitofusin result in a selective decrease in mtDNA(Delta)

150 Our data show that Marf and Mitofusins share an evolutionarily conserved role in mit

151 the PINK1/parkin pathway on a shared target mitofusin to maintain mitochondrial integrity.

152 T2A mutations, including a possible role for mitofusin ubiquitylation and degradation in CMT2A pathog

153 This leads to reduced ubiquitination of mitofusin via HUWE1, thereby promoting mitochondrial fus

154 how that endogenous VCP negatively regulates Mitofusin, which is required for outer mitochondrial mem

155 rough the ubiquitin-dependent degradation of Mitofusin, which itself causes PINK1/parkin mutant-like

156 Consistently, genetic deletion of mitofusins without concomitant expression of Parkin was