ライフサイエンスコーパス: mitofusin

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

2 gered by reduction of the pro-fusion protein Mitofusin.

3 active alleles with respect to regulation of Mitofusin.

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

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 small molecules to pharmacologically target mitofusins.

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

11 e function and involves large GTPases called mitofusins.

12 ochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86.

13 ized the impact of two recoding sites in the mitofusin 1 (MFN1) gene and showed their functional rele

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

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

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

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

18 mitochondrial integrity by interacting with mitofusin 1 (Mfn1).

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

20 The dynamin-like GTPases Mitofusin 1 and 2 (Mfn1 and Mfn2) are essential for mito

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

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

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

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

25 Re-activation of Opa1 and Mitofusin 1 in Drp1-knockout cells further connects mito

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

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

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

29 letely connect mitochondria because Opa1 and mitofusin 1, two other dynamin-related GTPases that medi

30 tion of a validated mitochondrial substrate, mitofusin 1.

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

32 rial morphology, how SLC25A46 interacts with mitofusin 1/2 and Opa1 to regulate membrane fusion is no

33 er and inner membrane dynamin family GTPases mitofusin 1/2 and optic atrophy 1 (Opa1).

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

35 Finally, we show that ELMOD2, ARL2, Mitofusins 1 and 2, Miros 1 and 2, and mitochondrial pho

36 s mitochondrial hyperfusion by up-regulating mitofusins 1 and 2, the predominant catalysts of mitocho

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

38 an ER tubule-shaping protein, interacts with Mitofusins 1/2 to mediate mitochondrial distribution thr

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

40 In cells, IB5 expression up-regulated Mitofusin-1 (Mfn1) and increased mitochondrial length.

41 een associated with these MERC contact sites mitofusin-1 (MFN1) and mitofusin-2 (MFN2) have been foun

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

43 al duration (APD) in cardiomyocytes from the Mitofusins-1/2 (Mfn1/Mfn2)-double-knockout (Mfn-DKO) com

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

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

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

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

48 dels, PC2 knockdown led to a 50% increase in mitofusin 2 (MFN2) expression, an outer mitochondrial me

49 tochondrial fusion, due in part to decreased mitofusin 2 (Mfn2) expression, contributes to unrestrict

50 s ROS production, thereby leading to reduced mitofusin 2 (MFN2) expression, decouple endoplasmic reti

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

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

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

54 Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease.

55 wn the neuronal mitochondrial fusion protein mitofusin 2 (MFN2) reduced the rates of axonal mitochond

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

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

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

59 Here, we show that mitofusin 2 (MFN2), a mitochondrial fusion protein, inte

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

61 Here, we characterized the function of mitofusin 2 (Mfn2), a mitochondrial outer membrane prote

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

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

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

65 nt is regulated by the mitochondrial protein mitofusin 2 (Mfn2), the expression of which is activated

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

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

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

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

70 functionally critical mitochondrial proteins mitofusin 2 and cyclophilin D, but not of transcription

71 inase alpha, which interacts with hepatocyte mitofusin 2 and induces protein disulfide isomerase acti

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

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

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

75 l network in neurons and examine the role of mitofusin 2 in maintaining the axonal mitochondrial netw

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

77 Mitofusin 2 is localized at both the outer membrane of m

78 Mutations in the MFN2 gene encoding Mitofusin 2 lead to the development of Charcot-Marie-Too

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

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

81 Down-regulation of the protein mitofusin 2 reduced the magnitude of [ATP](i) fluctuatio

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

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

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

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

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

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

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

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

90 us-1) and the mitochondrial dynamics protein Mitofusin 2, which confers increased susceptibility to i

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

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

93 y the p.Arg707Trp mutation in MFN2, encoding mitofusin 2.

94 with the endoplasmic reticulum (ER) protein mitofusin 2.

95 id metabolism in a transmembrane protein 205/mitofusin 2/protein disulfide isomerase-dependent pathwa

96 tein 1], OPA-1 [optic atrophy 1], and MFN 2 [mitofusin 2]), and oxidative phosphorylation (citrate sy

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

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

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

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

101 y, we observe that the mitochondrial protein Mitofusin-2 (Mfn2) co-localizes at the plasma membrane w

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

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

104 se MERC contact sites mitofusin-1 (MFN1) and mitofusin-2 (MFN2) have been found to be downregulated i

105 Here, we investigated the potential roles of Mitofusin-2 (MFN2) in thyroid cancer progression.

106 Mitofusin-2 (MFN2) is a dynamin-like GTPase that plays a

107 Mitofusin-2 (MFN2) is a mitochondrial outer-membrane pro

108 Mitofusin-2 (MFN2) is one of two ubiquitously expressed

109 onstrate that DIAPH1 interacts directly with Mitofusin-2 (MFN2) to shorten mitochondria-SR/ER distanc

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

111 chondrial functions cyclophilin D (CYPD) and mitofusin-2 (MFN2), leucine zipper EF-hand containing tr

112 N-specific CRISPR-Cas9-mediated knockdown of mitofusin-2 (Mfn2), the mitochondria-SR tethering GTPase

113 lear gene encoding the mitochondrial protein mitofusin-2 (MFN2).

114 Mitofusin-2 and calcineurin were positively correlated i

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

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

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

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

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

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

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

122 ate that the mitochondrial fusion machinery, Mitofusins, accumulate at ER MCSs where fusion occurs.

123 tinuous, but not intermittent, pharmacologic mitofusin activation delayed phenotype progression and l

124 Mechanistically, mitofusin activation increased mitochondrial motility, f

125 We find that mitofusin activation increases, whereas mitofusin inhibi

126 We observed that small molecule mitofusin activators corrected mitochondrial fragmentati

127 molecules that directly increase or inhibit mitofusins activity by modulating mitofusin conformation

128 l molecules to better understand the role of mitofusins activity in mitochondrial fusion, function, a

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

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

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

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

133 human triple-negative breast tumor tissues, mitofusin and myoglobin levels were positively correlate

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

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

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

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

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

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

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

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

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

143 Mitofusins are activated by conformational changes and s

144 Mitofusins are conserved GTPases essential for the fusio

145 Mitofusins are dynamin-related GTPases that are essentia

146 insights into the function and regulation of mitofusins as well as small molecules to pharmacological

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

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

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

150 Loss of the mitofusins causes severe mitochondrial dysfunction, comp

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

152 or inhibit mitofusins activity by modulating mitofusin conformations and oligomerization.

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

154 ed these mitochondrial dynamics by promoting mitofusin degradation.

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

156 lation and increases the rate of fusion in a mitofusin-dependent manner.

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

158 Similarly, mitofusin depletion in immortalized spermatocytes or ger

159 Depletion of Mitofusin (dMfn) or Opa1 led to dysfunctional mitochondr

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

161 We reveal that by promoting OXPHOS, mitofusins enable spermatogonial differentiation and a m

162 Mechanistically, increased mitofusin expression was due to myoglobin-dependent free

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

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

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

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

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

168 Whether mitofusin gene expression, and hence, mitochondrial netw

169 t-restricted deletion knock-out (dKO) of the mitofusin genes Mfn1 and Mfn2 (betaMfn1/2 dKO).

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

171 Deficiency in mitofusins impaired the electric activity of Agrp neuron

172 gs broaden our understanding of the roles of mitofusins in beta-cells, the potential contributions of

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

174 ulating fusogenic optic atrophy 1 (OPA1) and mitofusins in rat gastric mucosa.

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

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

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

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

179 Remarkably, mitofusin inhibition also induces minority mitochondrial

180 that mitofusin activation increases, whereas mitofusin inhibition decreases mitochondrial fusion and

181 of caspases (SMAC) mimetic is potentiated by mitofusin inhibition.

182 s that nucleotide-dependent self-assembly of Mitofusin is required after tethering to promote membran

183 at contributes to isoform-specific function (mitofusin isoform-specific region [MISR]).

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

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

186 liferation and tumor growth by up-regulating mitofusin levels.

187 With long-term mitofusin loss, all differentiating germ cell types are

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

189 ibited decreased tumor volume with increased mitofusin, markers of cell cycle arrest, and decreased p

190 sed Cx43 lateralization, suggesting that the mitofusins may impact on post-MI cardiac-arrhythmogenesi

191 study provides fundamental insight into how mitofusins mediate mitochondrial fusion and the ways the

192 ption of mitochondrial dynamics, by impeding mitofusin-mediated fusion or dynamin-like-protein-1-medi

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

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

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

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

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

198 Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is 15-20x over-represen

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

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

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

202 through the knockdown of the fusion protein mitofusin (MFN)-2 strongly reduced the mitochondrial Ca(

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

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

205 functions of mitochondrial fusion proteins, mitofusin (MFN)1 and MFN2, in modulating macrophage mito

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

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

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

209 We find that mitofusin MFN1, but not MFN2, is important for the activ

210 Because the mitofusins Mfn1 and Mfn2 are essential for mitochondrial

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

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

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

214 Acutely after depletion of mitofusins Mfn1 and Mfn2, spermatogenesis arrests due to

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

216 ein 1 (DRP1) that controls division, and the mitofusins (MFN1 and MFN2) and optic atrophy 1 (OPA1) dr

217 Mitofusins (Mfn1 and Mfn2) are outer mitochondrial membr

218 Mitofusins (Mfn1 and Mfn2) are the mitochondrial outer-m

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

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

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

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

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

224 Mitofusins (Mfns) are dynamin-related GTPases that media

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

226 ated membrane fusion, here we characterize a Mitofusin mutant variant etiologically linked to Charcot

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

228 Proteomics in fibroblasts reveals that mitofusin-null cells downregulate respiratory chain comp

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

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

231 tive control of fission and fusion proteins (mitofusins, OPA1 and DRP1) as well as through stretch-se

232 In vertebrates, two mitofusin paralogues, Mfn1 and Mfn2, are required for ef

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

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

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

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

237 Mitofusins reside on the outer mitochondrial membrane an

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

239 The mitofusins share a high degree of homology and have very

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

241 MISR confers unique fusion activity and mitofusin-specific nucleotide-dependent assembly propert

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

243 ector downstream of ARL2 and upstream of the mitofusins to promote mitochondrial fusion.

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

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

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

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

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