miR-30 Regulates Mitochondrial Fission through Targeting p53 and the Dynamin-Related Protein-1 Pathway
miRNAs participate in the regulation of apoptosis. However, it remains largely unknown as to how miRNAs are integrated into the apoptotic program. Mitochondrial fission is involved in the initiation of apoptosis. It is not yet clear whether miRNAs are able to regulate mitochondrial fission. Here we report that miR-30 family members are able to regulate apoptosis by targeting the mitochondrial fission machinery. Our data show that miR-30 family members can inhibit mitochondrial fission and the consequent apoptosis. In exploring the underlying molecular mechanism, we identified that miR-30 family members can suppress p53 expression. In response to the apoptotic stimulation, the expression levels of miR-30 family members were reduced, whereas p53 was upregulated. p53 transcriptionally activated the mitochondrial fission protein, dynamin-related protein-1 (Drp1). The latter conveyed the apoptotic signal of p53 by initiating the mitochondrial fission program. miR-30 family members inhibited mitochondrial fission through suppressing the expression of p53 and its downstream target Drp1. Our data reveal a novel model in which a miRNA can regulate apoptosis through targeting the mitochondrial fission machinery.
Vyšlo v časopise:
miR-30 Regulates Mitochondrial Fission through Targeting p53 and the Dynamin-Related Protein-1 Pathway. PLoS Genet 6(1): e32767. doi:10.1371/journal.pgen.1000795
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1000795
Souhrn
miRNAs participate in the regulation of apoptosis. However, it remains largely unknown as to how miRNAs are integrated into the apoptotic program. Mitochondrial fission is involved in the initiation of apoptosis. It is not yet clear whether miRNAs are able to regulate mitochondrial fission. Here we report that miR-30 family members are able to regulate apoptosis by targeting the mitochondrial fission machinery. Our data show that miR-30 family members can inhibit mitochondrial fission and the consequent apoptosis. In exploring the underlying molecular mechanism, we identified that miR-30 family members can suppress p53 expression. In response to the apoptotic stimulation, the expression levels of miR-30 family members were reduced, whereas p53 was upregulated. p53 transcriptionally activated the mitochondrial fission protein, dynamin-related protein-1 (Drp1). The latter conveyed the apoptotic signal of p53 by initiating the mitochondrial fission program. miR-30 family members inhibited mitochondrial fission through suppressing the expression of p53 and its downstream target Drp1. Our data reveal a novel model in which a miRNA can regulate apoptosis through targeting the mitochondrial fission machinery.
Zdroje
1. ParkSM
SchickelR
PeterME
2005 Nonapoptotic functions of FADD-binding death receptors and their signaling molecules. Curr Opin Cell Biol 17 610 616
2. HeL
HeX
LimLP
de StanchinaE
XuanZ
2007 A microRNA component of the p53 tumour suppressor network. Nature 447 1130 1134
3. NasserMW
DattaJ
NuovoG
KutayH
MotiwalaT
2008 Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem 283 33394 33405
4. AsanganiIA
RasheedSA
NikolovaDA
LeupoldJH
ColburnNH
2008 MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27 2128 2136
5. LofflerD
Brocke-HeidrichK
PfeiferG
StocsitsC
HackermullerJ
2007 Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood 110 1330 1333
6. McBrideHM
NeuspielM
WasiakS
2006 Mitochondria: more than just a powerhouse. Curr Biol 16 R551 560
7. TanakaA
YouleRJ
2008 A chemical inhibitor of DRP1 uncouples mitochondrial fission and apoptosis. Mol Cell 29 409 410
8. Cassidy-StoneA
ChipukJE
IngermanE
SongC
YooC
2008 Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell 14 193 204
9. KangPM
IzumoS
2000 Apoptosis and heart failure: A critical review of the literature. Circ Res 86 1107 1113
10. ElsasserA
SuzukiK
SchaperJ
2000 Unresolved issues regarding the role of apoptosis in the pathogenesis of ischemic injury and heart failure. J Mol Cell Cardiol 32 711 724
11. BarlucchiL
LeriA
DostalDE
FiordalisoF
TadaH
2001 Canine ventricular myocytes possess a renin-angiotensin system that is upregulated with heart failure. Circ Res 88 298 304
12. CrowMT
ManiK
NamYJ
KitsisRN
2004 The mitochondrial death pathway and cardiac myocyte apoptosis. Circ Res 95 957 970
13. KitsisRN
MannDL
2005 Apoptosis and the heart: a decade of progress. J Mol Cell Cardiol 38 1 2
14. SiwikDA
TzortzisJD
PimentalDR
ChangDL
PaganoPJ
1999 Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro. Circ Res 85 147 153
15. KwonSH
PimentelDR
RemondinoA
SawyerDB
ColucciWS
2003 H(2)O(2) regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways. J Mol Cell Cardiol 35 615 621
16. VousdenKH
2000 p53: death star. Cell 103 691 694
17. AgarwalML
TaylorWR
ChernovMV
ChernovaOB
StarkGR
1998 The p53 network. J Biol Chem 273 1 4
18. LevineAJ
1997 p53, the cellular gatekeeper for growth and division. Cell 88 323 331
19. MiyashitaT
ReedJC
1995 Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80 293 299
20. YuJ
ZhangL
HwangPM
KinzlerKW
VogelsteinB
2001 PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell 7 673 682
21. NakanoK
VousdenKH
2001 PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 7 683 694
22. FrankS
GaumeB
Bergmann-LeitnerES
LeitnerWW
RobertEG
2001 The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell 1 515 525
23. IkedaS
KongSW
LuJ
BispingE
ZhangH
2007 Altered microRNA expression in human heart disease. Physiol Genomics 31 367 373
24. van RooijE
SutherlandLB
ThatcherJE
DiMaioJM
NaseemRH
2008 Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A 105 13027 13032
25. TangX
GalJ
ZhuangX
WangW
ZhuH
2007 A simple array platform for microRNA analysis and its application in mouse tissues. Rna 13 1803 1822
26. WinterJ
JungS
KellerS
GregoryRI
DiederichsS
2009 Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11 228 234
27. CarthewRW
SontheimerEJ
2009 Origins and Mechanisms of miRNAs and siRNAs. Cell 136 642 655
28. BartelDP
2009 MicroRNAs: target recognition and regulatory functions. Cell 136 215 233
29. el-DeiryWS
KernSE
PietenpolJA
KinzlerKW
VogelsteinB
1992 Definition of a consensus binding site for p53. Nat Genet 1 45 49
30. CribbsJT
StrackS
2007 Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep 8 939 944
31. WasiakS
ZuninoR
McBrideHM
2007 Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J Cell Biol 177 439 450
32. BrasM
YusteVJ
RoueG
BarbierS
SanchoP
2007 Drp1 mediates caspase-independent type III cell death in normal and leukemic cells. Mol Cell Biol 27 7073 7088
33. JiangP
DuW
HeeseK
WuM
2006 The Bad guy cooperates with good cop p53: Bad is transcriptionally up-regulated by p53 and forms a Bad/p53 complex at the mitochondria to induce apoptosis. Mol Cell Biol 26 9071 9082
34. LiPF
DietzR
von HarsdorfR
1999 p53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochrome c-independent apoptosis blocked by Bcl-2. EMBO J 18 6027 6036
35. PolyakK
XiaY
ZweierJL
KinzlerKW
VogelsteinB
1997 A model for p53-induced apoptosis. Nature 389 300 305
36. BennettM
MacdonaldK
ChanSW
LuzioJP
SimariR
1998 Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science 282 290 293
37. SchulerM
Bossy-WetzelE
GoldsteinJC
FitzgeraldP
GreenDR
2000 p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release. J Biol Chem 275 7337 7342
38. DuistersRF
TijsenAJ
SchroenB
LeendersJJ
LentinkV
2009 miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res 104 170 178, 176p following 178
39. PetroccaF
VecchioneA
CroceCM
2008 Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res 68 8191 8194
40. SchickelR
BoyerinasB
ParkSM
PeterME
2008 MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27 5959 5974
41. MendellJT
2008 miRiad roles for the miR-17-92 cluster in development and disease. Cell 133 217 222
42. TanakaM
ItoH
AdachiS
AkimotoH
NishikawaT
1994 Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circ Res 75 426 433
43. LongX
BoluytMO
HipolitoML
LundbergMS
ZhengJS
1997 p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes. J Clin Invest 99 2635 2643
44. WebsterKA
DischerDJ
KaiserS
HernandezO
SatoB
1999 Hypoxia-activated apoptosis of cardiac myocytes requires reoxygenation or a pH shift and is independent of p53. J Clin Invest 104 239 252
45. ShizukudaY
ButtrickPM
GeenenDL
BorczukAC
KitsisRN
1998 beta-adrenergic stimulation causes cardiocyte apoptosis: influence of tachycardia and hypertrophy. Am J Physiol 275 H961 968
46. FanGC
ChuG
MittonB
SongQ
YuanQ
2004 Small heat-shock protein Hsp20 phosphorylation inhibits beta-agonist-induced cardiac apoptosis. Circ Res 94 1474 1482
47. KajsturaJ
CigolaE
MalhotraA
LiP
ChengW
1997 Angiotensin II induces apoptosis of adult ventricular myocytes in vitro. J Mol Cell Cardiol 29 859 870
48. SaitoS
HiroiY
ZouY
AikawaR
TokoH
2000 beta-Adrenergic pathway induces apoptosis through calcineurin activation in cardiac myocytes. J Biol Chem 275 34528 34533
49. ReeveJL
DuffyAM
O' BrienT
SamaliA
2005 Don't lose heart–therapeutic value of apoptosis prevention in the treatment of cardiovascular disease. J Cell Mol Med 9 609 622
50. StammC
FriehsI
CowanDB
Cao-DanhH
ChoiYH
2002 Dopamine treatment of postischemic contractile dysfunction rapidly induces calcium-dependent pro-apoptotic signaling. Circulation 106 I290 298
51. BuenoOF
LipsDJ
KaiserRA
WilkinsBJ
DaiYS
2004 Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction. Circ Res 94 91 99
52. van EmpelVP
BertrandAT
van der NagelR
KostinS
DoevendansPA
2005 Downregulation of apoptosis-inducing factor in harlequin mutant mice sensitizes the myocardium to oxidative stress-related cell death and pressure overload-induced decompensation. Circ Res 96 e92 e101
53. AoyamaT
MatsuiT
NovikovM
ParkJ
HemmingsB
2005 Serum and glucocorticoid-responsive kinase-1 regulates cardiomyocyte survival and hypertrophic response. Circulation 111 1652 1659
54. TothA
JeffersJR
NicksonP
MinJY
MorganJP
2006 Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. Am J Physiol Heart Circ Physiol 291 H52 60
55. MurtazaI
WangHX
FengX
AleninaN
BaderM
2008 Down-regulation of catalase and oxidative modification of protein kinase CK2 lead to the failure of apoptosis repressor with caspase recruitment domain to inhibit cardiomyocyte hypertrophy. J Biol Chem 283 5996 6004
56. LiPF
DietzR
von HarsdorfR
1999 Superoxide induces apoptosis in cardiomyocytes, but proliferation and expression of transforming growth factor-beta1 in cardiac fibroblasts. FEBS Lett 448 206 210
57. LiYZ
LuDY
TanWQ
WangJX
LiPF
2008 p53 initiates apoptosis by transcriptionally targeting the anti-apoptotic protein ARC. Mol Cell Biol 28 564 574
58. LiPF
LiJ
MullerEC
OttoA
DietzR
2002 Phosphorylation by protein kinase CK2: a signaling switch for the caspase-inhibiting protein ARC. Mol Cell 10 247 258
59. SandigV
BrandK
HerwigS
LukasJ
BartekJ
1997 Adenovirally transferred p16INK4/CDKN2 and p53 genes cooperate to induce apoptotic tumor cell death. Nat Med 3 313 319
60. SzakST
MaysD
PietenpolJA
2001 Kinetics of p53 Binding to Promoter Sites In Vivo. Mol Cell Biol 21 3375 3386
61. LanzaG
FerracinM
GafaR
VeroneseA
SpizzoR
2007 mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer. Mol Cancer 6 54
62. LauP
VerrierJD
NielsenJA
JohnsonKR
NotterpekL
2008 Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J Neurosci 28 11720 11730
63. WangJX
LiQ
LiPF
2009 Apoptosis repressor with caspase recruitment domain contributes to the chemotherapy resistance by abolishing mitochondrial fission mediated by dynamin-related protein-1. Cancer Res 69 492 500
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2010 Číslo 1
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- A Major Role of the RecFOR Pathway in DNA Double-Strand-Break Repair through ESDSA in
- Kidney Development in the Absence of and Requires
- The Werner Syndrome Protein Functions Upstream of ATR and ATM in Response to DNA Replication Inhibition and Double-Strand DNA Breaks
- Alternative Epigenetic Chromatin States of Polycomb Target Genes