ライフサイエンスコーパス: SIRT3

1 ated with reduced levels of renal sirtuin 3 (SIRT3).

2 tion of the mitochondrial sirtuin sirtuin-3 (SIRT3).

3 sirt2, which is homologous to human sir2 and sirt3.

4 HKL depend on activation of the deacetylase Sirt3.

5 that deacetylation depends on mitochondrial SIRT3.

6 ke and cell proliferation, are controlled by SIRT3.

7 tribute to the tumor-suppressive activity of SIRT3.

8 cellent selectivity for SIRT2 over SIRT1 and SIRT3.

9 vity of SOD2 is regulated by the deacetylase SIRT3.

10 ormation, our findings reveal a dual role of SirT3.

11 wild-type or lacked the protein deacetylase SIRT3.

12 m mouse liver mitochondria in the absence of SIRT3.

13 alignant phenotype observed in cells lacking Sirt3.

14 and high isozyme selectivity over SIRT1 and SIRT3.

15 al protein acetylation in response to CR and SIRT3, (2) identify three biochemically distinct classes

16 Our SIRT3-5 interaction network provides a framework for dis

17 ion of genes involved in metabolism, whereas Sirt3-5 reside in the mitochondrial matrix and regulate

18 Mitochondrial sirtuins, SIRT3-5, are NAD(+)-dependent deacylases and ADP-ribosyl

19 Three sirtuins, SIRT3-5, localize to mitochondria.

20 Although Sirtuin 3 (SIRT3), a mitochondrially enriched deacetylase and activ

21 ective effects by up-regulating the level of Sirt3, a member of Sirtuin family protein located in mit

22 We also showed that Sirt3 ablation sensitized mice to NASH, whereas adenovir

23 se mice, in which SIRT1 activity is low, and SIRT3 acetylation at Lys(57) inhibits its deacetylase ac

24 mitochondrial SIRT3 functions by inhibiting SIRT3 acetylation may offer a new therapeutic approach f

25 Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with

26 xidation by complex I is a crucial event for SIRT3 activation by RSV.

27 SIRT3 activation could be a potential therapy for DOX-in

28 This effect might be mediated by SIRT3 activation, controlling mitochondrial reactive oxy

29 phic studies of 11c, 28, and 31 bound in the SIRT3 active site revealed that the common carboxamide b

30 this study, we examined whether the loss of Sirt3 activity increases vascular oxidative stress becau

31 Increased Sirt3 activity is associated with reduced acetylation of

32 e assessed by using immunohistochemistry for SIRT3 activity via acetylated MnSOD(K68) Murine AEC SIRT

33 Indeed, even when SIRT3 activity was abolished, activation of mitochondria

34 did not lead to significant modifications in SIRT3 activity, the major mitochondrial lysine deacetyla

35 Our study suggests that SIRT3 acts as a tumor suppressor in B cell malignancies,

36 There is controversy as to whether SIRT3 acts as an oncogene or a tumor suppressor, and her

37 Our data reveal that SirT3 acts to orchestrate two pathways, the antioxidant

38 These observations suggest that SirT3 acts to sort moderately stressed from irreversibly

39 We confirmed the SIRT-RELB-SIRT3 adaptation link to mitochondrial bioenergetics in

40 AICAR nor ALCAR treatment prevented death in Sirt3-/- AKI mice.

41 o NASH, whereas adenoviral overexpression of Sirt3 alleviated the NASH phenotype in AhR-transgenic mi

42 s by a process that requires skeletal muscle SIRT3-AMPK-GLUT4 signaling.

43 Sirtuin 3 (SIRT3), an important regulator of energy metabolism and

44 ND#115926) displayed increased activation of SIRT3 and AMP-activated protein kinase.

45 el with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase.

46 ctivity via acetylated MnSOD(K68) Murine AEC SIRT3 and cleaved caspase-9 (CC-9) expression were assay

47 wn substrates and sites that are targeted by SIRT3 and establishes SIRT3 as a global regulator of mit

48 results in decreased deacetylase activity of SIRT3 and further leads to reduction in cellular NAD(+)

49 cation of SIRT3, and is reversed with excess SIRT3 and NAD(+) in vitro.

50 y attenuated mutant Htt-induced depletion of SIRT3 and protected cells from mutant Htt.

51 re, Y381 phosphorylation of PDP1 dissociates SIRT3 and recruits ACAT1 to PDC.

52 sphorylation of PDP1 dissociates deacetylase SIRT3 and recruits acetyltransferase ACAT1 to PDC, resul

53 high selectivity toward SIRT2 over SIRT1 and SIRT3 and represent an important starting point for the

54 SIRT3 and SIRT5 are NAD-consuming enzymes that are poten

55 ystal structures of the ternary complexes of SIRT3 and SIRT5 bound to a peptide substrate and carba-N

56 ious human sirtuins, including SIRT1, SIRT2, SIRT3 and SIRT5.

57 and DOX induced a dose-dependent decrease in SIRT3 and SOD2 expression in H9c2 cardiomyocytes.

58 ing mitochondria-targeted catalase prevented Sirt3 and SOD2 impairment and attenuated hypertension.

59 on was markedly increased in Sirt3-knockout (Sirt3(-/)(-)) and SOD2-depleted (SOD2(+/)(-)) mice in re

60 pressure and improved vasorelaxation both in Sirt3(-/-) and wild-type mice.

61 ion, including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), and Nrf-1.

62 showed increased expression of Pgc1alpha and Sirt3, and improved mitochondrial respiration, compared

63 DH and direct carbonyl group modification of SIRT3, and is reversed with excess SIRT3 and NAD(+) in v

64 cient decrotonylases, and that SIRT1, SIRT2, SIRT3, and SIRT4 can remove lipoic acid.

65 of the SIRT2 acyl pocket to those of SIRT1, SIRT3, and SIRT6 reveals that the acyl pockets of SIRT1-

66 orms, silent information regulator (SIRT) 1, SIRT3, and SIRT6, play an essential role in the regulati

67 focus primarily on mammalian sirtuins SIRT1, SIRT3, and SIRT6, the three sirtuins for which the most

68 eak effects on other sirtuins such as SIRT1, SIRT3, and yeast Sir2.

69 poptosis in wild-type mice were amplified in Sirt3(-/-) animals.

70 Here we demonstrate that Sirt1, Sirt2, and Sirt3 are expressed in enucleate platelets.

71 The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are conside

72 , the cytosolic Sirt2, and the mitochondrial Sirt3 are robust deacetylases, whereas the other sirtuin

73 s that are targeted by SIRT3 and establishes SIRT3 as a global regulator of mitochondrial protein ace

74 ave identified the mitochondrial deacetylase SIRT3 as a key regulator of mitochondrial reactive oxyge

75 cancer, and as such, these results implicate SIRT3 as a potential regulator of IDH2-dependent functio

76 eover, we identified mitochondrial ACAT1 and SIRT3 as the upstream acetyltransferase and deacetylase,

77 as significantly increased in the absence of SIRT3 (at least twofold).

78 Our results suggest that overexpression of SIRT3 attenuates DOX-induced ROS production, and this ma

79 and metabolic conditions further inactivate Sirt3 because of increased NADH (nicotinamide adenine di

80 In healthy mitochondria, a pool of SIRT3 binds ATP synthase, but upon matrix pH reduction w

81 vers a fundamental role for sequestration of SIRT3 by ATP synthase in mitochondrial homeostasis.

82 chanism operates to induce its own inhibitor SIRT3 by PGC-1beta.

83 in 129SJ/wild-type and SIRT3-knockout mice (Sirt3(-/-) ) by using fibrosis scoring and lung collagen

84 We found that Sirt1, Sirt2, and Sirt3 can catalyze the hydrolysis of lysine crotonylated

85 Sirtuins, particularly SIRT1 and SIRT3, can be activated by fasting and further exhibit t

86 t that HKL is a pharmacological activator of Sirt3 capable of blocking, and even reversing, the cardi

87 (3,4,5)-triphosphate binding and activation, SIRT3 controls reactive oxygen species-mediated Akt acti

88 Here, we show that SIRT3 controls transformation of fibroblasts into myofib

89 ollowing increased expression, mitochondrial SIRT3 deacetylase activates the rate-limiting tricarboxy

90 ionary roles that the mitochondria-localized SIRT3 deacetylase and SIRT5 desuccinylase have in the ma

91 caused by inhibition of the NAD(+)-dependent SIRT3 deacetylase.

92 is a process that can be antagonized by the SIRT3 deacetylase.

93 SIRT3 deacetylated and activated GSK3beta and thereby bl

94 In response to cAMP signaling, SIRT3 deacetylated and activated leucine-rich protein 13

95 lorie restriction, mitochondrial deacetylase Sirt3 deacetylates and activates IDH2, thereby regulatin

96 Sirtuin 3 (SIRT3) deacetylates and regulates many mitochondrial pro

97 letal muscle revealed that a major target of Sirt3 deacetylation is the E1alpha subunit of PDH (PDH E

98 l long-chain acyl-CoA dehydrogenase, a known SIRT3 deacetylation target; improved fatty acid beta-oxi

99 Overexpression of SIRT3 decreased proliferation and diminished the Warburg

100 SIRT3 deficiency caused induction of TGF-beta1 expressio

101 These data suggest a novel role for SIRT3 deficiency in mediating AEC mtDNA damage, apoptosi

102 We reasoned that SIRT3 deficiency occurs in fibrotic lungs and thereby au

103 SIRT3 deficiency promotes lung fibrosis by augmenting al

104 Importantly, SIRT3 deficiency results in a defect in cellular iron ho

105 and diminished the Warburg-like phenotype in SIRT3-deficient cell lines, and this effect is largely d

106 y and mutagenesis analyses indicated that in SIRT3-deficient cells OPA1 was acetylated at lysine 926

107 -lowering effect of nitrite was abolished in SIRT3-deficient human skeletal muscle cells, and in SIRT

108 Moreover, Sirt3-deficient mice given cisplatin experienced more se

109 FL SIRT3 degradation is mediated by the ubiquitin-proteasom

110 Moreover, SIRT3-dependent activation of OPA1 contributed to the pr

111 data support the hypothesis that IR triggers SIRT3-dependent deacetylation of ceramide synthases and

112 This higher NAD(+) level initiates a SIRT3-dependent increase in the mitochondrial substrate

113 n and differentiation to myofibroblasts in a Sirt3-dependent manner.

114 rts NAFLD by inducing a sirtuin (SIRT)1- and SIRT3-dependent mitochondrial unfolded protein response,

115 ible factor 1 (HIF1), which drove redox- and SIRT3-dependent stabilization of HIF1 in normoxic condit

116 Sirt3 depletion increased SOD2 acetylation, elevated mit

117 Sirtuin 3 (SIRT3) detoxifies mitochondrial reactive oxygen species,

118 etic diets may be mediated, in part, through SIRT3-directed blunting of NLRP3 inflammasome assembly a

119 in the mitochondria of SIRT3-null mice, and SIRT3 directly deacetylates the ceramide synthases in a

120 nt loss of mitochondrial membrane potential, SIRT3 dissociates.

121 re assayed by immunoblotting with or without SIRT3 enforced expression or silencing.

122 al protein acetylation, including MnSOD(K68) SIRT3 enforced expression reduced oxidant-induced AEC OG

123 show, for the first time, that mice lacking SIRT3 exhibit increased insulin resistance due to defect

124 Mice deficient in SIRT3 exhibited severe osteopenia owing to increased num

125 nt agent acetyl-l-carnitine (ALCAR) restored SIRT3 expression and activity, improved renal function,

126 r SIRT1 guides RELB to differentially induce SIRT3 expression and also increases mitochondrial biogen

127 Our data suggest that diminished Sirt3 expression and redox inactivation of Sirt3 lead to

128 SIRT3 expression from RANKL induction depended on the tr

129 Importantly, loss of SIRT3 expression in keratinocytes increased superoxide l

130 In fasting mice, Sirt3 expression is decreased in skeletal muscle resulti

131 Our studies demonstrate that SIRT3 expression is down-regulated during keratinocyte d

132 Indeed, SIRT3 expression is negatively correlated with TfR1 expr

133 hat HKL is present in mitochondria, enhances Sirt3 expression nearly twofold and suggest that HKL may

134 nistration of DOX to mice suppressed cardiac SIRT3 expression, and DOX induced a dose-dependent decre

135 reatic tumors, which correlates with reduced SIRT3 expression.

136 s-322, were also efficiently deacetylated by SIRT3 following chemical acetylation.

137 Lastly, depletion of SIRT3 from malignant B cell lines resulted in greater su

138 Deacetylation by SIRT3 fully restored maximum IDH2 activity.

139 More importantly, Sirt3 functions as a decrotonylase to regulate histone K

140 ism through IRP1 regulation and suggest that SIRT3 functions as a tumor suppressor, in part, by modul

141 Improving mitochondrial SIRT3 functions by inhibiting SIRT3 acetylation may offe

142 Overexpression of Sirt3 further prevented LPS-induced pericyte loss and va

143 Importantly, Sirt3 gene ablation reduced the brain injury after IR.

144 the NAD(+)-dependent deacetylase sirtuin 3 (SIRT3) generated rhythms in the acetylation and activity

145 LPS significantly reduced the expression of SIRT3, HIF-2alpha and Notch3 in the lung.

146 Mice were exposed to LPS, expression of Sirt3, HIF-2alpha, Notch3 and angiopoietins/Tie-2, peric

147 Sirt3 impairment reduces the activity of a key mitochond

148 But a physiological role of SIRT3 in bone metabolism is not known.

149 Inhibition of SirT3 in cells undergoing proteotoxic stress severely im

150 Our data uncover a novel role of SIRT3 in cellular iron metabolism through IRP1 regulatio

151 nd CerS6, but not CerS4, are associated with SIRT3 in cerebral mitochondria.

152 This novel role of SirT3 in established tumors represents an essential mech

153 we establish a novel role for mitochondrial SIRT3 in HD pathogenesis and discovered a natural produc

154 These results show that the absence of SIRT3 in HFD-fed mice causes profound impairments in ins

155 e, a short hairpin RNA-mediated knockdown of SIRT3 in human melanoma cells resulted in (i) a decrease

156 This study investigated the involvement of SIRT3 in LPS-induced pericyte loss and microvascular dys

157 supporting the pro-proliferative function of SIRT3 in melanoma.

158 lps orchestrate nuclear oxidant defenses and Sirt3 in mice led to a clear age-related loss of SNc dop

159 iosynthesis and suggest an important role of SIRT3 in mitochondrial dysfunction and brain injury afte

160 Our study demonstrates the importance of SIRT3 in preserving vascular integrity by targeting peri

161 However, the presence of full-length (FL) SIRT3 in the nucleus and its functional importance remai

162 These findings identify a new role for SIRT3 in the suppression of epidermal differentiation vi

163 novel role of the mitochondrial deacetylase SirT3 in the UPR(mt).

164 significance of the mitochondrial sirtuin 3 (SIRT3) in melanoma.

165 Overexpression of wild-type SIRT3 increased cardiolipin levels and rescued mitochond

166 e mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in associa

167 Indeed, genetic deletion of Sirt3 increased oxidative stress and decreased the membr

168 ted the mitochondrial sirtuin deacetylase 3 (Sirt3), increased SOD2 acetylation, and thereby decrease

169 ctor-1alpha pathway, suggesting that loss of SIRT3 increases proliferation via ROS-dependent but hypo

170 DH activity resulting from reduced levels of Sirt3 induces a switch of skeletal muscle substrate util

171 n receptor-related receptor alpha), and that SIRT3 inhibited the differentiation by interfering with

172 These findings suggest that SIRT3 inhibition and consequent protein hyperacetylation

173 these studies highlight a novel mechanism of SIRT3 involvement in modulating mitochondrial ceramide b

174 Here we show that SIRT3 is a key regulatory molecule to maintain bone home

175 SIRT3 is a member of the Sir2 family of NAD(+)-dependent

176 ylation sites, and (3) provide evidence that SIRT3 is a prominent regulator in CR adaptation by coord

177 Our results suggest that a mitochondrial SIRT3 is an intrinsic inhibitor for RANKL-mediated osteo

178 Sirt3 is an NAD(+)-dependent deacetylase that regulates

179 Recent studies indicated that SIRT3 is decreased in 87% of breast cancers, implying th

180 SIRT3 is hyperacetylated in aged and obese mice, in whic

181 Together, our results indicate that SIRT3 is protective against AKI and suggest that enhanci

182 Since SirT3 is reported to act as a tumor suppressor during tr

183 rapid deacetylation of matrix proteins, and SIRT3 is required for recovery of membrane potential.

184 Here we show that SIRT3 is reversibly acetylated in the mitochondria and u

185 primary and immortalized human melanocytes, SIRT3 is significantly overexpressed in multiple human m

186 oying human tissue microarray, we found that SIRT3 is significantly upregulated in clinical melanoma

187 Here, we report that nuclear FL SIRT3 is subjected to rapid degradation under conditions

188 n deacetylating and altering the function of SIRT3 is unknown.

189 Sirtuin-3 (SIRT3) is a class III lysine deacetylase that is localiz

190 Sirtuin-3 (Sirt3) is a mitochondrial deacetylase that could mediate

191 Sirtuin 3 (SIRT3) is an NAD(+)-dependent mitochondrial protein deac

192 The mitochondrial sirtuin 3 (SIRT3) is involved in suppressing the onset of multiple

193 were not observed with an acetylation-mimic SIRT3-K57Q mutant.

194 ression of SIRT3 or an acetylation-defective SIRT3-K57R mutant in diet-induced obese mice decreased a

195 In SIRT3 knock-out bone marrow-derived macrophages, NLRP3 a

196 nse to nutrient deprivation in wild-type and SIRT3 knock-out mice.

197 he inflammasome in wild-type mice but not in SIRT3 knock-out mice.

198 Sirt3 knockout in vivo and Sirt3 knockdown in myoblasts in vitro induced hyperacety

199 Finally, we found that SIRT3 knockdown significantly inhibited tumorigenesis in

200 Permeabilized muscle fibers from HFD-fed SIRT3 knockout (KO) mice showed that tricarboxylic acid

201 We found that Sirt3 knockout (KO) mice with age develop tissue fibrosi

202 Sirt3 knockout in vivo and Sirt3 knockdown in myoblasts

203 strated increased LCAD lysine acetylation in SIRT3 knockout mice concomitant with reduced LCAD activi

204 eficient human skeletal muscle cells, and in SIRT3 knockout mice fed a high-fat diet, as well.

205 S AND Hypertension was markedly increased in Sirt3-knockout (Sirt3(-/)(-)) and SOD2-depleted (SOD2(+/

206 xposure was evaluated in 129SJ/wild-type and SIRT3-knockout mice (Sirt3(-/-) ) by using fibrosis scor

207 e potential of SNc dopaminergic neurons from Sirt3 knockouts.

208 chondria is decreased in muscle from HFD-fed SIRT3 KO mice, suggesting decreased HKII activity.

209 Insulin action was not impaired in the lean SIRT3 KO mice.

210 macrophage cytokines, including IL-1beta, in SIRT3 KO mice.

211 rometry of mitochondrial lysates from WT and Sirt3 KO skeletal muscle revealed that a major target of

212 duces ROS synthesis in wild type, but not in Sirt3-KO cells.

213 d Sirt3 expression and redox inactivation of Sirt3 lead to SOD2 inactivation and contributes to the p

214 Inactivation of SIRT3 leads to elevated Skp2 acetylation, which leads to

215 Deletion of Sirt3 led to impaired glucose oxidation in muscle, which

216 l otoprotective small molecule via elevating Sirt3 levels and Sirt3 may be of therapeutic value in ha

217 and that, in response to prolonged fasting, SIRT3 levels modulate mitochondrial protein folding.

218 in SOD2 acetylation and 1.4-fold decrease in Sirt3 levels, whereas SOD2 expression was not affected.

219 ells expressing mutant Htt displayed reduced SIRT3 levels.

220 SIRT3 loss increases reactive oxygen species production,

221 anipulation of the expression or activity of Sirt3 may also represent a novel approach to manage NASH

222 mall molecule via elevating Sirt3 levels and Sirt3 may be of therapeutic value in hair cell protectio

223 These SIRT3-mediated beneficial effects were not observed with

224 brain ischemia/reperfusion (IR) showed that SIRT3-mediated deacetylation of ceramide synthases incre

225 mmasome components but, rather, occurred via SIRT3-mediated deacetylation of mitochondrial SOD2, lead

226 In fasted liver, SIRT3-mediated increases in substrate flux depend on oxi

227 late the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control.

228 ective effects of viniferin, suggesting that SIRT3 mediates the neuroprotection of viniferin.

229 Sirtuin 3 (SIRT3) mediates histone protein post-translational modif

230 duced blood pressure in wild-type but not in Sirt3(-/-) mice, whereas an SOD2 mimetic, (2-[2,2,6,6-te

231 Osteoclast precursors from Sirt3-/- mice underwent increased osteoclastogenesis in

232 r injury in WT animals, but had no effect in Sirt3-/- mice.

233 esults suggest that increasing mitochondrial SIRT3 might be considered as a new therapeutic approach

234 mic, IDH2(K413R) variant was able to protect Sirt3(-/-) mouse embryonic fibroblasts from oxidative st

235 SIRT3 null cells contain high levels of iron and lose ir

236 Moreover, SIRT3 null mice exhibit higher levels of iron and TfR1 e

237 6 are hyperacetylated in the mitochondria of SIRT3-null mice, and SIRT3 directly deacetylates the cer

238 SIRT3-null mouse embryonic fibroblasts produced signific

239 restingly, the negative regulatory effect of SIRT3 on NLRP3 was not due to transcriptional control or

240 Adenovirus-mediated expression of SIRT3 or an acetylation-defective SIRT3-K57R mutant in d

241 We also found that siRNA knockdown of SIRT3 or SOD2 increased NLRP3 supercomplex formation and

242 Moreover, Sirt3-/- osteoclast precursors reduced AMP-activated pro

243 liver, kidney, and lungs but not whole-body SIRT3-overexpressing mice.

244 SIRT3 overexpression decreases TfR1 expression by inhibi

245 Deacetylation with recombinant SIRT3 partially restored activity.

246 r in B cell malignancies, and activating the SIRT3 pathway might represent a novel therapeutic approa

247 Thus, Sirt3 plays an important role in skeletal muscle mitocho

248 rpose of this study was to determine whether SIRT3 prevents DOX-induced mitochondrial ROS production.

249 Overexpression of SIRT3 prevents microtubule disassembly and apoptosis eli

250 d by antimicrotubule agents and knockdown of SIRT3 prevents the protective effects of NAD(+) on micro

251 nversely, forced exogenous overexpression of SIRT3 promoted an increase in proliferative potential of

252 In summary, these data indicated that SIRT3 promotes mitochondrial function not only by regula

253 udies suggest that an age-related decline in Sirt3 protective function is a major factor underlying i

254 This suggests that SIRT3 protects against dietary insulin resistance by fac

255 Asbestos and H2O2 diminished AEC SIRT3 protein expression and increased mitochondrial pro

256 ymphoma patient samples, we found that lower SIRT3 protein expression was associated with worse overa

257 Further, SIRT3 protein expression was reduced in chronic lymphocy

258 Conversely, overexpression of Sirt3 reduced Ang-2 expression and increased Ang-1/Tie-2

259 ther, these data demonstrate that NAD(+) and SIRT3 regulate microtubule polymerization and the effica

260 Using mass spectrometry, we identified SIRT3-regulated lysine residues in LRP130 that generated

261 These data show that SIRT3 regulates acetylation on multiple proteins, often

262 Here, we report that mitochondrial SIRT3 regulates cellular iron metabolism by modulating I

263 Herein, we report that SIRT3 regulates mitochondrial ceramide biosynthesis via

264 SIRT3 regulates the acetylation level and enzymatic acti

265 findings reveal an unexpected mechanism for SIRT3 regulation via SIRT1-mediated deacetylation.

266 engineered cells, indicate that pH-dependent SIRT3 release requires H135 in the ATP5O subunit of ATP

267 ga maritima Sir2 and to moderately inhibited Sirt3 requires NAD(+), alone or together with acetylpept

268 ctional studies demonstrated that absence of SIRT3 rescued the IR-induced blockade of the electron tr

269 = 3.6, 2.7, and 4.0 nM for SIRT1, SIRT2, and SIRT3, respectively).

270 tured human tubular cells, cisplatin reduced SIRT3, resulting in mitochondrial fragmentation, while r

271 Investigation of the SIRT3 role in mitochondrial response to brain ischemia/r

272 Sirt3 silencing experiments confirmed that Sirt3-ROS signaling axis mediated hair cell protection a

273 II-induced hypertension was associated with Sirt3 S-glutathionylation, acetylation of vascular SOD2,

274 hydrogen peroxide scavenger ebselen, reduced Sirt3 S-glutathionylation, diminished SOD2 acetylation,

275 Knockdown of SIRT3 significantly inhibited viniferin-mediated AMP-act

276 Sirt3 silencing experiments confirmed that Sirt3-ROS sig

277 lation, mtDNA damage, and apoptosis, whereas SIRT3 silencing promoted these effects.

278 RATIONALE: Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% by 65 years

279 SIRT3 (sirtuin 3) is the major deacetylase within the mi

280 We demonstrate that Hsp10 is a functional SIRT3 substrate and that, in response to prolonged fasti

281 ed with reduced acetylation of mitochondrial Sirt3 substrates, MnSOD and oligomycin-sensitivity confe

282 acetylation on LCAD and determine sirtuin 3 (SIRT3) target sites, we chemically acetylated recombinan

283 idues Lys-318 and Lys-322 were identified as SIRT3-targeted lysines.

284 e data sets with our compendium of predicted Sirt3 targets.

285 he unknown cellular mechanisms controlled by Sirt3, that have previously been considered solely as a

286 Sirtuin 3 (SIRT3), the primary mitochondrial deacetylase, has been

287 rly twofold and suggest that HKL may bind to Sirt3 to further increase its activity.

288 ctive against AKI and suggest that enhancing SIRT3 to improve mitochondrial dynamics has potential as

289 These data reveal a new role of SIRT3 to negatively regulate aging-associated tissue fib

290 The ability of SIRT3 to protect cells from oxidative stress was depende

291 Intriguingly, knockout of Sirt3 upregulated Ang-2, but downregulated Tie-2 and HIF

292 and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively.

293 The mitochondrial deacetylase SIRT3 was capable of deacetylating OPA1 and elevating it

294 trated that the NAD(+)-dependent deacetylase SIRT3 was essential for the prevention of age-related he

295 Increased activity of SIRT3 was evidenced by normalization of the increased ac

296 cts were absent when a deacetylase-deficient SIRT3 was expressed in H9c2 cells.

297 Deletion of Pgc1alpha or Sirt3, which are key regulators of OXPHOS, abrogated Tre

298 ogenic effects of nutrients were reversed by SIRT3, which deacetylates lys(101) acetylation.

299 l acetylation state, via genetic deletion of SIRT3, will amplify the deleterious effects of a high-fa

300 hondrial fragmentation, while restoration of SIRT3 with AICAR and ALCAR improved cisplatin-induced mi