Skip to content
2000
Volume 32, Issue 9
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Mitochondria are the energy factories of cells, and their functions are closely related to cell homeostasis. The mitochondrial unfolded protein response (mtUPR) is a newly discovered mechanism for regulating mitochondrial homeostasis. When unfolded/misfolded proteins accumulate in mitochondria, the mitochondria release signals that regulate the transcription of certain proteins in the nucleus, thereby inducing the correct folding or degradation of proteins in mitochondria. Many studies have also shown that an abnormality of mtUPR is closely related to the occurrence and development of diseases. Here, we summarized the pathways regulating mtUPR signaling and reviewed the research progress on mtUPR in diseases. Finally, we summarized the currently identified agonists and inhibitors of the mtUPR and discussed the potential of the mtUPR as a therapeutic target for diseases.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0929867331666230822095924
2023-10-31
2025-05-31
Loading full text...

Full text loading...

References

  1. YangM. LiC. SunL. Mitochondria-Associated Membranes (MAMs): A novel therapeutic target for treating metabolic syndrome.Curr. Med. Chem.20212871347136210.2174/1875533XMTA0iNDEoz32048952
    [Google Scholar]
  2. FlisV.V. DaumG. Lipid transport between the endoplasmic reticulum and mitochondria.Cold Spring Harb. Perspect. Biol.201356a01323510.1101/cshperspect.a01323523732475
    [Google Scholar]
  3. Bravo-SaguaR. ParraV. López-CrisostoC. DíazP. QuestA.F. LavanderoS. Calcium transport and signaling in mitochondria.Compr. Physiol.20177262363410.1002/cphy.c16001328333383
    [Google Scholar]
  4. RossiA. PizzoP. FiladiR. Calcium, mitochondria and cell metabolism: A functional triangle in bioenergetics.Biochim. Biophys. Acta Mol. Cell Res.2019186671068107810.1016/j.bbamcr.2018.10.01630982525
    [Google Scholar]
  5. NareshN.U. HaynesC.M. Signaling and regulation of the mitochondrial unfolded protein response.Cold Spring Harb. Perspect. Biol.2019116a03394410.1101/cshperspect.a03394430617048
    [Google Scholar]
  6. OmuraT. Mitochondria-targeting sequence, a multi-role sorting sequence recognized at all steps of protein import into mitochondria.J. Biochem.199812361010101610.1093/oxfordjournals.jbchem.a0220369603986
    [Google Scholar]
  7. ChenC. WangK. ZhangH. ZhouH.J. ChenY. MinW. A unique SUMO-Interacting motif of trx2 is critical for its mitochondrial presequence processing and anti-oxidant activity.Front. Physiol.201910108910.3389/fphys.2019.0108931555141
    [Google Scholar]
  8. MachJ. PoliakP. MatuškováA. ŽárskýV. JanataJ. LukešJ. TachezyJ. An advanced system of the mitochondrial processing peptidase and core protein family in Trypanosoma brucei and multiple origins of the core i subunit in eukaryotes.Genome Biol. Evol.20135586087510.1093/gbe/evt05623563972
    [Google Scholar]
  9. KitadaS. ItoA. Electrostatic recognition of matrix targeting signal by mitochondrial processing peptidase.J. Biochem.2001129115516110.1093/oxfordjournals.jbchem.a00282711134970
    [Google Scholar]
  10. CallegariS. DennerleinS. Sensing the stress: A role for the UPR(mt) and UPR(am) in the quality control of mitochondria.Front. Cell Dev. Biol.201863110.3389/fcell.2018.0003129644217
    [Google Scholar]
  11. Poveda-HuertesD. TaskinA.A. DhaouadiI. MyketinL. MaradaA. HabernigL. BüttnerS. VögtleF.N. Increased mitochondrial protein import and cardiolipin remodelling upon early mtUPR.PLoS Genet.2021177e100966410.1371/journal.pgen.100966434214073
    [Google Scholar]
  12. Poveda-HuertesD. MaticS. MaradaA. HabernigL. LichevaM. MyketinL. GilsbachR. Tosal-CastanoS. PapinskiD. MulicaP. KretzO. KücükköseC. TaskinA.A. HeinL. KraftC. BüttnerS. MeisingerC. VögtleF.N. An early mtUPR: Redistribution of the nuclear transcription factor rox1 to mitochondria protects against intramitochondrial proteotoxic aggregates.Mol. Cell2020771180188.e910.1016/j.molcel.2019.09.02631630969
    [Google Scholar]
  13. CaiY. ShenH. WengH. WangY. CaiG. ChenX. YeQ. Overexpression of PGC-1α influences the mitochondrial unfolded protein response (mtUPR) induced by MPP+ in human SH-SY5Y neuroblastoma cells.Sci. Rep.20201011044410.1038/s41598‑020‑67229‑632591623
    [Google Scholar]
  14. ColemanO.I. HallerD. ER stress and the UPR in shaping intestinal tissue homeostasis and immunity.Front. Immunol.201910282510.3389/fimmu.2019.0282531867005
    [Google Scholar]
  15. KennedyD. SamaliA. JägerR. Methods for studying ER stress and UPR markers in human cells.Methods Mol. Biol.2015129231810.1007/978‑1‑4939‑2522‑3_125804744
    [Google Scholar]
  16. WalczakA. GradzikK. KabzinskiJ. Przybylowska-SygutK. MajsterekI. The role of the ER-Induced UPR pathway and the efficacy of its inhibitors and inducers in the inhibition of tumor progression.Oxid. Med. Cell. Longev.2019201911510.1155/2019/572971030863482
    [Google Scholar]
  17. MelberA. HaynesC.M. UPRmt regulation and output: A stress response mediated by mitochondrial-nuclear communication.Cell Res.201828328129510.1038/cr.2018.1629424373
    [Google Scholar]
  18. LinY.F. SchulzA.M. PellegrinoM.W. LuY. ShahamS. HaynesC.M. Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response.Nature2016533760341641910.1038/nature1798927135930
    [Google Scholar]
  19. MartinusR.D. GarthG.P. WebsterT.L. CartwrightP. NaylorD.J. HøjP.B. HoogenraadN.J. Selective induction of mitochondrial chaperones in response to loss of the mitochondrial genome.Eur. J. Biochem.199624019810310.1111/j.1432‑1033.1996.0098h.x8797841
    [Google Scholar]
  20. WuZ. SenchukM.M. DuesD.J. JohnsonB.K. CooperJ.F. LewL. MachielaE. SchaarC.E. DeJongeH. BlackwellT.K. Van RaamsdonkJ.M. Mitochondrial unfolded protein response transcription factor ATFS-1 promotes longevity in a long-lived mitochondrial mutant through activation of stress response pathways.BMC Biol.201816114710.1186/s12915‑018‑0615‑330563508
    [Google Scholar]
  21. ChenY.G. YueH.T. ZhangZ.Z. YuanF.H. BiH.T. YuanK. WengS.P. HeJ.G. ChenY.H. Identification and characterization of a mitochondrial unfolded protein response transcription factor ATFS-1 in Litopenaeus vannamei.Fish Shellfish Immunol.20165414415210.1016/j.fsi.2015.10.01926481519
    [Google Scholar]
  22. PeñaS. ShermanT. BrookesP.S. NehrkeK. The mitochondrial unfolded protein response protects against anoxia in caenorhabditis elegans.PLoS One2016117e015998910.1371/journal.pone.015998927459203
    [Google Scholar]
  23. NargundA.M. PellegrinoM.W. FioreseC.J. BakerB.M. HaynesC.M. Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.Science2012337609458759010.1126/science.122356022700657
    [Google Scholar]
  24. SooS.K. Van RaamsdonkJ.M. High confidence ATFS-1 target genes for quantifying activation of the mitochondrial unfolded protein response.MicroPubl Biol.202120211010.17912/micropub.biology.00048434693215
    [Google Scholar]
  25. SteenK.A. XuH. BernlohrD.A. FABP4/aP2 regulates macrophage redox signaling and inflammasome activation via control of UCP2.Mol. Cell. Biol.2017372e00282-1610.1128/MCB.00282‑1627795298
    [Google Scholar]
  26. ZhaoQ. WangJ. LevichkinI.V. StasinopoulosS. RyanM.T. HoogenraadN.J. A mitochondrial specific stress response in mammalian cells.EMBO J.200221174411441910.1093/emboj/cdf44512198143
    [Google Scholar]
  27. AldridgeJ.E. HoribeT. HoogenraadN.J. Discovery of genes activated by the mitochondrial unfolded protein response (mtUPR) and cognate promoter elements.PLoS One200729e87410.1371/journal.pone.000087417849004
    [Google Scholar]
  28. FioreseC.J. SchulzA.M. LinY.F. RosinN. PellegrinoM.W. HaynesC.M. The transcription factor ATF5 mediates a mammalian mitochondrial UPR.Curr. Biol.201626152037204310.1016/j.cub.2016.06.00227426517
    [Google Scholar]
  29. TeskeB.F. FusakioM.E. ZhouD. ShanJ. McClintickJ.N. KilbergM.S. WekR.C. CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.Mol. Biol. Cell201324152477249010.1091/mbc.e13‑01‑006723761072
    [Google Scholar]
  30. WengH. MaY. ChenL. CaiG. ChenZ. ZhangS. YeQ. A new vision of mitochondrial unfolded protein response to the sirtuin family.Curr. Neuropharmacol.202018761362310.2174/1570159X1866620012316500231976838
    [Google Scholar]
  31. PapaL. GermainD. Estrogen receptor mediates a distinct mitochondrial unfolded protein response.J. Cell Sci.201112491396140210.1242/jcs.07822021486948
    [Google Scholar]
  32. RadkeS. ChanderH. SchäferP. MeissG. KrügerR. SchulzJ.B. GermainD. Mitochondrial protein quality control by the proteasome involves ubiquitination and the protease Omi.J. Biol. Chem.200828319126811268510.1074/jbc.C80003620018362145
    [Google Scholar]
  33. Pimenta de CastroI. CostaA.C. LamD. TufiR. FedeleV. MoisoiN. DinsdaleD. DeasE. LohS.H.Y. MartinsL.M. Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster.Cell Death Differ.20121981308131610.1038/cdd.2012.522301916
    [Google Scholar]
  34. PapaL. GermainD. SirT3 regulates the mitochondrial unfolded protein response.Mol. Cell. Biol.201434469971010.1128/MCB.01337‑1324324009
    [Google Scholar]
  35. CelestiniV. TezilT. RussoL. FasanoC. SaneseP. ForteG. PesericoA. Lepore SignorileM. LongoG. De RasmoD. SignorileA. GadaletaR.M. ScialpiN. TeraoM. GarattiniE. CoccoT. VillaniG. MoschettaA. GrossiV. SimoneC. Uncoupling FoxO3A mitochondrial and nuclear functions in cancer cells undergoing metabolic stress and chemotherapy.Cell Death Dis.20189223110.1038/s41419‑018‑0336‑029445193
    [Google Scholar]
  36. TaoR. VassilopoulosA. ParisiadouL. YanY. GiusD. Regulation of MnSOD enzymatic activity by Sirt3 connects the mitochondrial acetylome signaling networks to aging and carcinogenesis.Antioxid. Redox Signal.201420101646165410.1089/ars.2013.548223886445
    [Google Scholar]
  37. LuoS. YangM. ZhaoH. HanY. LiuY. XiongX. ChenW. LiC. SunL. Mitochondrial DNA-dependent inflammation in kidney diseases.Int. Immunopharmacol.202210710863710.1016/j.intimp.2022.10863735279513
    [Google Scholar]
  38. YangM. WangX. HanY. LiC. WeiL. YangJ. ChenW. ZhuX. SunL. Targeting the NLRP3 inflammasome in diabetic nephropathy.Curr. Med. Chem.202128428810882410.2174/092986732866621070515310934225600
    [Google Scholar]
  39. YangM. HanY. LuoS. XiongX. ZhuX. ZhaoH. JiangN. XiaoY. WeiL. LiC. YangJ. SunL. MAMs protect against ectopic fat deposition and lipid-related kidney damage in DN patients.Front. Endocrinol.20211260958010.3389/fendo.2021.60958033679616
    [Google Scholar]
  40. YangM. LiC. YangS. XiaoY. ChenW. GaoP. JiangN. XiongS. WeiL. ZhangQ. YangJ. ZengL. SunL. Mitophagy: A novel therapeutic target for treating DN.Curr. Med. Chem.202128142717272810.2174/092986732766620100615265633023427
    [Google Scholar]
  41. Rojas-MoralesP. León-ContrerasJ.C. Granados-PinedaJ. Hernández-PandoR. GonzagaG. Sánchez-LozadaL.G. Osorio-AlonsoH. Pedraza-ChaverriJ. TapiaE. Protection against renal ischemia and reperfusion injury by short-term time-restricted feeding involves the mitochondrial unfolded protein response.Free Radic. Biol. Med.2020154758310.1016/j.freeradbiomed.2020.04.02532376457
    [Google Scholar]
  42. ZhangB. ShenX.L. LiangR. LiY. HuangK. ZhaoC. LuoY. XuW. Protective role of the mitochondrial Lon protease 1 in ochratoxin A-induced cytotoxicity in HEK293 cells.J. Proteomics201410115416810.1016/j.jprot.2014.02.01724565693
    [Google Scholar]
  43. LiC. ChenW. ZhengL. ZhangB. YangX. ZhangQ. WangN. WangY. YangJ. ShaJ. ZhouZ. LiX. LiY. ShenX.L. Ameliorative effect of ursolic acid on ochratoxin A-induced renal cytotoxicity mediated by Lonp1/Aco2/Hsp75.Toxicon201916814114610.1016/j.toxicon.2019.07.01431356822
    [Google Scholar]
  44. GongW. SongJ. LiangJ. MaH. WuW. ZhangY. YangL. HuangS. JiaZ. ZhangA. Reduced Lon protease 1 expression in podocytes contributes to the pathogenesis of podocytopathy.Kidney Int.202199485486910.1016/j.kint.2020.10.02533181155
    [Google Scholar]
  45. SunZ. ZhengW. TengJ. FangZ. LinC. Resveratrol reduces kidney injury in a rat model of uremia and is associated with increased expression of heat shock protein 70 (Hsp70).Med. Sci. Monit.202026e91908610.12659/MSM.91908632040471
    [Google Scholar]
  46. El-GamasyM. El-SadekA. FakhreldinA. KamelA. ElbeheryE. Heat shock protein 60 as a biomarker for acute kidney injury secondary to septic shock in pediatric patients, Egyptian multicenter experience.Saudi J. Kidney Dis. Transpl.201829485286210.4103/1319‑2442.23965130152422
    [Google Scholar]
  47. KimJ. KimD.S. ParkM.J. ChoH.J. ZervosA.S. BonventreJ.V. ParkK.M. Omi/HtrA2 protease is associated with tubular cell apoptosis and fibrosis induced by unilateral ureteral obstruction.Am. J. Physiol. Renal Physiol.20102986F1332F134010.1152/ajprenal.00737.200920219823
    [Google Scholar]
  48. FaccioL. FuscoC. ChenA. MartinottiS. BonventreJ.V. ZervosA.S. Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia.J. Biol. Chem.200027542581258810.1074/jbc.275.4.258110644717
    [Google Scholar]
  49. ZhangH. MenziesK.J. AuwerxJ. The role of mitochondria in stem cell fate and aging.Development20181458dev14342010.1242/dev.14342029654217
    [Google Scholar]
  50. ChiangJ.L. ShuklaP. PagidasK. AhmedN.S. KarriS. GunnD.D. HurdW.W. SinghK.K. Mitochondria in ovarian aging and reproductive longevity.Ageing Res. Rev.20206310116810.1016/j.arr.2020.10116832896666
    [Google Scholar]
  51. JanikiewiczJ. SzymańskiJ. MalinskaD. Patalas-KrawczykP. MichalskaB. DuszyńskiJ. GiorgiC. BonoraM. DobrzynA. WieckowskiM.R. Mitochondria-associated membranes in aging and senescence: Structure, function, and dynamics.Cell Death Dis.20189333210.1038/s41419‑017‑0105‑529491385
    [Google Scholar]
  52. PatelJ. BaptisteB.A. KimE. HussainM. CroteauD.L. BohrV.A. DNA damage and mitochondria in cancer and aging.Carcinogenesis202041121625163410.1093/carcin/bgaa11433146705
    [Google Scholar]
  53. KudryavtsevaA.V. KrasnovG.S. DmitrievA.A. AlekseevB.Y. KardymonO.L. SadritdinovaA.F. FedorovaM.S. PokrovskyA.V. MelnikovaN.V. KaprinA.D. MoskalevA.A. SnezhkinaA.V. Mitochondrial dysfunction and oxidative stress in aging and cancer.Oncotarget2016729448794490510.18632/oncotarget.982127270647
    [Google Scholar]
  54. LeeH.C. WeiY.H. Mitochondria and aging.Adv. Exp. Med. Biol.201294231132710.1007/978‑94‑007‑2869‑1_1422399429
    [Google Scholar]
  55. BraticA. LarssonN.G. The role of mitochondria in aging.J. Clin. Invest.2013123395195710.1172/JCI6412523454757
    [Google Scholar]
  56. JangJ.Y. BlumA. LiuJ. FinkelT. The role of mitochondria in aging.J. Clin. Invest.201812893662367010.1172/JCI12084230059016
    [Google Scholar]
  57. AngeliS. FoulgerA. ChamoliM. PeirisT.H. GerencserA. ShahmirzadiA.A. AndersenJ. LithgowG. The mitochondrial permeability transition pore activates the mitochondrial unfolded protein response and promotes aging.eLife202110e6345310.7554/eLife.6345334467850
    [Google Scholar]
  58. MerkwirthC. JovaisaiteV. DurieuxJ. MatilainenO. JordanS.D. QuirosP.M. SteffenK.K. WilliamsE.G. MouchiroudL. TronnesS.U. MurilloV. WolffS.C. ShawR.J. AuwerxJ. DillinA. Two conserved histone demethylases regulate mitochondrial stress-induced longevity.Cell201616551209122310.1016/j.cell.2016.04.01227133168
    [Google Scholar]
  59. Owusu-AnsahE. SongW. PerrimonN. Muscle mitohormesis promotes longevity via systemic repression of insulin signaling.Cell2013155369971210.1016/j.cell.2013.09.02124243023
    [Google Scholar]
  60. MouchiroudL. HoutkooperR.H. MoullanN. KatsyubaE. RyuD. CantóC. MottisA. JoY.S. ViswanathanM. SchoonjansK. GuarenteL. AuwerxJ. The NAD(+)/Sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling.Cell2013154243044110.1016/j.cell.2013.06.01623870130
    [Google Scholar]
  61. CordeiroA.V. PerucaG.F. BragaR.R. BrícolaR.S. LenhareL. SilvaV.R.R. AnarumaC.P. KatashimaC.K. CrisolB.M. BarbosaL.T. SimabucoF.M. da SilvaA.S.R. CintraD.E. de MouraL.P. PauliJ.R. RopelleE.R. High-intensity exercise training induces mitonuclear imbalance and activates the mitochondrial unfolded protein response in the skeletal muscle of aged mice.Geroscience20214331513151810.1007/s11357‑020‑00246‑532737758
    [Google Scholar]
  62. AbdelwahidE. StulpinasA. KalvelyteA. Effective agents targeting the mitochondria and apoptosis to protect the heart.Curr. Pharm. Des.20172381153116610.2174/138161282266616122915012028034298
    [Google Scholar]
  63. WangW. SheuS.S. Unsolved mysteries and controversies of mitochondria in the heart- A virtual special issue in JMCC: Part III.J. Mol. Cell. Cardiol.2020144A1A210.1016/j.yjmcc.2020.06.00932603737
    [Google Scholar]
  64. MasuzawaA. BlackK.M. PacakC.A. EricssonM. BarnettR.J. DrummC. SethP. BlochD.B. LevitskyS. CowanD.B. McCullyJ.D. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury.Am. J. Physiol. Heart Circ. Physiol.20133047H966H98210.1152/ajpheart.00883.201223355340
    [Google Scholar]
  65. WeixlerV. LapuscaR. GranglG. GuarientoA. SaeedM.Y. CowanD.B. del NidoP.J. McCullyJ.D. FriehsI. Autogenous mitochondria transplantation for treatment of right heart failure.J. Thorac. Cardiovasc. Surg.20211621e111e12110.1016/j.jtcvs.2020.08.01132919774
    [Google Scholar]
  66. BuggerH. PfeilK. Mitochondrial ROS in myocardial ischemia reperfusion and remodeling.Biochim. Biophys. Acta Mol. Basis Dis.20201866716576810.1016/j.bbadis.2020.16576832173461
    [Google Scholar]
  67. ZhouM. YuY. LuoX. WangJ. LanX. LiuP. FengY. JianW. Myocardial ischemia-reperfusion injury: Therapeutics from a mitochondria-centric perspective.Cardiology2021146678179210.1159/00051887934547747
    [Google Scholar]
  68. DiaM. GomezL. ThibaultH. TessierN. LeonC. ChouabeC. DucreuxS. Gallo-BonaN. TubbsE. BendridiN. ChanonS. LerayA. BelmudesL. CoutéY. KurdiM. OvizeM. RieussetJ. PaillardM. Reduced reticulum–mitochondria Ca2+ transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy.Basic Res. Cardiol.202011567410.1007/s00395‑020‑00835‑733258101
    [Google Scholar]
  69. BerthiaumeJ.M. KurdysJ.G. MunteanD.M. RoscaM.G. Mitochondrial NAD(+)/NADH redox state and diabetic cardiomyopathy.Antioxid. Redox Signal.201930337539810.1089/ars.2017.741529073779
    [Google Scholar]
  70. JiH. WangJ. MuidD. SongW. JiangY. ZhouH. FUNDC1 activates the mitochondrial unfolded protein response to preserve mitochondrial quality control in cardiac ischemia/reperfusion injury.Cell. Signal.20229211024910.1016/j.cellsig.2022.11024935051611
    [Google Scholar]
  71. SmyrniasI. GrayS.P. OkonkoD.O. SawyerG. ZoccaratoA. CatibogN. LópezB. GonzálezA. RavassaS. DíezJ. ShahA.M. Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload.J. Am. Coll. Cardiol.201973141795180610.1016/j.jacc.2018.12.08730975297
    [Google Scholar]
  72. WangY. JasperH. ToanS. MuidD. ChangX. ZhouH. Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury.Redox Biol.20214510204910.1016/j.redox.2021.10204934174558
    [Google Scholar]
  73. XuM. XueR.Q. LuY. YongS.Y. WuQ. CuiY.L. ZuoX.T. YuX.J. ZhaoM. ZangW.J. Choline ameliorates cardiac hypertrophy by regulating metabolic remodelling and UPRmt through SIRT3-AMPK pathway.Cardiovasc. Res.2019115353054510.1093/cvr/cvy21730165480
    [Google Scholar]
  74. LinL. KimS.C. WangY. GuptaS. DavisB. SimonS.I. Torre-AmioneG. KnowltonA.A. HSP60 in heart failure: Abnormal distribution and role in cardiac myocyte apoptosis.Am. J. Physiol. Heart Circ. Physiol.20072934H2238H224710.1152/ajpheart.00740.200717675567
    [Google Scholar]
  75. GuillonB. BulteauA.L. Wattenhofer-DonzéM. SchmuckerS. FriguetB. PuccioH. DrapierJ.C. BoutonC. Frataxin deficiency causes upregulation of mitochondrial Lon and ClpP proteases and severe loss of mitochondrial Fe-S proteins.FEBS J.200927641036104710.1111/j.1742‑4658.2008.06847.x19154341
    [Google Scholar]
  76. CookS.A. SugdenP.H. ClerkA. Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease.J. Mol. Cell. Cardiol.19993181429143410.1006/jmcc.1999.097910423341
    [Google Scholar]
  77. LiuX. LeiJ. WangK. MaL. LiuD. DuY. WuY. ZhangS. WangW. MaX. LiuH. Mitochondrial Omi/HtrA2 promotes caspase activation through cleavage of HAX-1 in aging heart.Rejuvenation Res.201720318319210.1089/rej.2016.186127998213
    [Google Scholar]
  78. O’MalleyJ. KumarR. InigoJ. YadavaN. ChandraD. Mitochondrial stress response and cancer.Trends Cancer20206868870110.1016/j.trecan.2020.04.00932451306
    [Google Scholar]
  79. ChenH. ZhangD.M. ZhangZ.P. LiM.Z. WuH.F. SIRT3-mediated mitochondrial unfolded protein response weakens breast cancer sensitivity to cisplatin.Genes Genomics202143121433144410.1007/s13258‑021‑01145‑534338986
    [Google Scholar]
  80. WangG. FanY. CaoP. TanK. Insight into the mitochondrial unfolded protein response and cancer: Opportunities and challenges.Cell Biosci.20221211810.1186/s13578‑022‑00747‑035180892
    [Google Scholar]
  81. ZhuL. LuoX. FuN. ChenL. Mitochondrial unfolded protein response: A novel pathway in metabolism and immunity.Pharmacol. Res.202116810560310.1016/j.phrs.2021.10560333838292
    [Google Scholar]
  82. WeidlingI.W. SwerdlowR.H. Mitochondria in Alzheimer’s disease and their potential role in Alzheimer’s proteostasis.Exp. Neurol.202033011332110.1016/j.expneurol.2020.11332132339611
    [Google Scholar]
  83. PellegrinoM.W. HaynesC.M. Mitophagy and the mitochondrial unfolded protein response in neurodegeneration and bacterial infection.BMC Biol.20151312210.1186/s12915‑015‑0129‑125857750
    [Google Scholar]
  84. DastidarS.G. PhamM.T. MitchellM.B. YeomS.G. JordanS. ChangA. SopherB.L. La SpadaA.R. 4E-BP1 protects neurons from misfolded protein stress and Parkinson’s disease toxicity by inducing the mitochondrial unfolded protein response.J. Neurosci.202040458734874510.1523/JNEUROSCI.0940‑20.202033046555
    [Google Scholar]
  85. LeeM.J. JangY. ZhuJ. NamgungE. GoD. SeoC. JuX. CuiJ. LeeY.L. KangH. KimH. ChungW. HeoJ.Y. Auraptene enhances junction assembly in cerebrovascular endothelial cells by promoting resilience to mitochondrial stress through activation of antioxidant enzymes and mtUPR.Antioxidants202110347510.3390/antiox1003047533802930
    [Google Scholar]
  86. KalvalaA.K. YerraV.G. SherkhaneB. GunduC. ArruriV. KumarR. KumarA. Chronic hyperglycemia impairs mitochondrial unfolded protein response and precipitates proteotoxicity in experimental diabetic neuropathy: Focus on LonP1 mediated mitochondrial regulation.Pharmacol. Rep.20207261627164410.1007/s43440‑020‑00147‑632720218
    [Google Scholar]
  87. YungH.W. ColleoniF. DommettE. Cindrova-DaviesT. KingdomJ. MurrayA.J. BurtonG.J. Noncanonical mitochondrial unfolded protein response impairs placental oxidative phosphorylation in early-onset preeclampsia.Proc. Natl. Acad. Sci.201911636181091811810.1073/pnas.190754811631439814
    [Google Scholar]
  88. ShamalnasabM. GravelS.P. St-PierreJ. BretonL. JägerS. AguilaniuH. A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response.Aging Cell2018176e1283010.1111/acel.1283030192051
    [Google Scholar]
  89. HouM. BaoW. GaoY. ChenJ. SongG. Honokiol improves cognitive impairment in APP/PS1 mice through activating mitophagy and mitochondrial unfolded protein response.Chem. Biol. Interact.202235110974110.1016/j.cbi.2021.10974134752757
    [Google Scholar]
  90. ShenY. DingM. XieZ. LiuX. YangH. JinS. XuS. ZhuZ. WangY. WangD. XuL. ZhouX. WangP. BiJ. Activation of mitochondrial unfolded protein response in SHSY5Y expressing APP cells and APP/PS1 mice.Front. Cell. Neurosci.20201356810.3389/fncel.2019.0056831969805
    [Google Scholar]
  91. XuM. BiX. HeX. YuX. ZhaoM. ZangW. Inhibition of the mitochondrial unfolded protein response by acetylcholine alleviated hypoxia/reoxygenation-induced apoptosis of endothelial cells.Cell Cycle201615101331134310.1080/15384101.2016.116098527111378
    [Google Scholar]
  92. CaiG. LinF. WuD. LinC. ChenH. WeiY. WengH. ChenZ. WuM. HuangE. YeZ. YeQ. Rosmarinic acid inhibits mitochondrial damage by alleviating unfolded protein response.Front. Pharmacol.20221385997810.3389/fphar.2022.85997835652041
    [Google Scholar]
/content/journals/cmc/10.2174/0929867331666230822095924
Loading
/content/journals/cmc/10.2174/0929867331666230822095924
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keyword(s): aging; ATFS-1; ATP; kidney diseases; mitochondria; mtUPR
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test