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PGC-1α participates in tumor chemoresistance by regulating glucose metabolism and mitochondrial function

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Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Chemotherapy resistance is the main reason for the failure of cancer treatment. The mechanism of drug resistance is complex and diverse. In recent years, the role of glucose metabolism and mitochondrial function in cancer resistance has gathered considerable interest. The increase in metabolic plasticity of cancer cells’ mitochondria and adaptive changes to the mitochondrial function are some of the mechanisms through which cancer cells resist chemotherapy. As a key molecule regulating the mitochondrial function and glucose metabolism, PGC-1α plays an indispensable role in cancer progression. However, the role of PGC-1α in chemotherapy resistance remains controversial. Here, we discuss the role of PGC-1α in glucose metabolism and mitochondrial function and present a comprehensive overview of PGC-1α in chemotherapy resistance.

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Abbreviations

PGC-1α:

Proliferator-activated receptor gamma (PPAR γ) coactivator-1α

HK2:

Hexokinase 2

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

P-gp:

P-glycoprotein

PDK:

Pyruvate dehydrogenase kinase

ATP:

Adenosine triphosphate

PKM2:

Pyruvate kinase M2

ROS:

Reactive oxygen species

ERR:

Estrogen-related receptor

MEF:

Myoblast enhancer 2

LDH:

Lactate dehydrogenase

MOMP:

Mitochondrial outer membrane permeability

Drp1:

Dynamin-relatedprotein 1

MFN2:

Mitofusin2

OPA1:

Optic atrophy 1

UCP2:

Uncoupling protein 2

Nrf:

Subcellular localization of nuclear factor E2-related factor

TFAM:

Mitochondrial transcription factor A

References

  1. Siegel RL, Miller KD, Jemal A (2020) Cancer statistics. CA Cancer J Clin 70:7–30. https://doi.org/10.3322/caac.21590

    Article  Google Scholar 

  2. Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT (1984) Landmark article Sept. 21, 1946: Nitrogen mustard therapy. Use of methyl-bis(beta-chloroethyl)amine hydrochloride and tris(beta-chloroethyl)amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. By Louis S. Goodman, Maxwell M. Wintrobe, William Dameshek, Morton J. Goodman, Alfred Gilman and Margaret T. McLennan Jama 251:2255–2261. https://doi.org/10.1001/jama.251.17.2255

    Article  CAS  Google Scholar 

  3. Rivera Vargas T, Apetoh L (2017) Danger signals: chemotherapy enhancers? Immunol Rev 280:175–193. https://doi.org/10.1111/imr.12581

    Article  CAS  Google Scholar 

  4. Abdel-Wahab AF, Mahmoud W, Al-Harizy RM (2019) Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy. Pharmacol Res 150:104511. https://doi.org/10.1016/j.phrs.2019.104511

    Article  CAS  Google Scholar 

  5. Reina-Campos M, Moscat J, Diaz-Meco M (2017) Metabolism shapes the tumor microenvironment. Curr Opin Cell Biol 48:47–53. https://doi.org/10.1016/j.ceb.2017.05.006

    Article  CAS  Google Scholar 

  6. Zhang XY, Zhang M, Cong Q, Zhang MX, Zhang MY, Lu YY, Xu CJ (2018) Hexokinase 2 confers resistance to cisplatin in ovarian cancer cells by enhancing cisplatin-induced autophagy. Int J Biochem Cell Biol 95:9–16. https://doi.org/10.1016/j.biocel.2017.12.010

    Article  CAS  Google Scholar 

  7. Chen J, Yoshinaga M, Garbinski LD, Rosen BP (2016) Synergistic interaction of glyceraldehydes-3-phosphate dehydrogenase and ArsJ, a novel organoarsenical efflux permease, confers arsenate resistance. Mol Microbiol 100:945–953. https://doi.org/10.1111/mmi.13371

    Article  CAS  Google Scholar 

  8. Anderson RG, Ghiraldeli LP, Pardee TS (2018) Mitochondria in cancer metabolism, an organelle whose time has come? Biochim Biophys Acta Rev Cancer 1870:96–102. https://doi.org/10.1016/j.bbcan.2018.05.005

    Article  CAS  Google Scholar 

  9. Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, Shu Y (2019) Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer 18:157. https://doi.org/10.1186/s12943-019-1089-9

    Article  Google Scholar 

  10. Condon KJ, Orozco JM, Adelmann CH, Spinelli JB, van der Helm PW, Roberts JM, Kunchok T, Sabatini DM (2021) Genome-wide CRISPR screens reveal multitiered mechanisms through which mTORC1 senses mitochondrial dysfunction. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.2022120118

    Article  Google Scholar 

  11. Cruz-Bermúdez A, Laza-Briviesca R, Vicente-Blanco RJ, García-Grande A, Coronado MJ, Laine-Menéndez S, Palacios-Zambrano S, Moreno-Villa MR, Ruiz-Valdepeñas AM, Lendinez C, Romero A, Franco F, Calvo V, Alfaro C, Acosta PM, Salas C, Garcia JM, Provencio M (2019) Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition. Free Radic Biol Med 135:167–181. https://doi.org/10.1016/j.freeradbiomed.2019.03.009

    Article  CAS  Google Scholar 

  12. Christie EL, Pattnaik S, Beach J, Copeland A, Rashoo N, Fereday S, Hendley J, Alsop K, Brady SL, Lamb G, Pandey A, deFazio A, Thorne H, Bild A, Bowtell DDL (2019) Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer. Nat Commun 10:1295. https://doi.org/10.1038/s41467-019-09312-9

    Article  CAS  Google Scholar 

  13. Luo X, Liao C, Quan J, Cheng C, Zhao X, Bode AM, Cao Y (2019) Posttranslational regulation of PGC-1α and its implication in cancer metabolism. Int J Cancer 145:1475–1483. https://doi.org/10.1002/ijc.32253

    Article  CAS  Google Scholar 

  14. Krämer AI, Handschin C (2019) How epigenetic modifications drive the expression and mediate the action of PGC-1α in the regulation of metabolism. Int J Mol Sci. https://doi.org/10.3390/ijms20215449

    Article  Google Scholar 

  15. Xiao B, Deng X, Ng EY, Tio M, Prakash KM, Au WL, Tan L, Zhao Y, Tan EK (2017) GWAS-linked PPARGC1A variant in Asian patients with essential tremor. Brain 140:e24. https://doi.org/10.1093/brain/awx027

    Article  Google Scholar 

  16. Tavares CDJ, Aigner S, Sharabi K, Sathe S, Mutlu B, Yeo GW, Puigserver P (2020) Transcriptome-wide analysis of PGC-1α-binding RNAs identifies genes linked to glucagon metabolic action. Proc Natl Acad Sci USA 117:22204–22213. https://doi.org/10.1073/pnas.2000643117

    Article  CAS  Google Scholar 

  17. Shen L, Sun B, Sheng J, Yu S, Li Y, Xu H, Su J, Sun L (2018) PGC1α promotes cisplatin resistance in human ovarian carcinoma cells through upregulation of mitochondrial biogenesis. Int J Oncol 53:404–416. https://doi.org/10.3892/ijo.2018.4401

    Article  CAS  Google Scholar 

  18. Konieczkowski DJ, Johannessen CM, Garraway LA (2018) A convergence-based framework for cancer drug resistance. Cancer Cell 33:801–815. https://doi.org/10.1016/j.ccell.2018.03.025

    Article  CAS  Google Scholar 

  19. Cree IA, Charlton P (2017) Molecular chess? Hallmarks of anti-cancer drug resistance. BMC Cancer 17:10. https://doi.org/10.1186/s12885-016-2999-1

    Article  CAS  Google Scholar 

  20. Haider T, Pandey V, Banjare N, Gupta PN, Soni V (2020) Drug resistance in cancer: mechanisms and tackling strategies. Pharmacol Rep 72:1125–1151. https://doi.org/10.1007/s43440-020-00138-7

    Article  Google Scholar 

  21. Shahar N, Larisch S (2020) Inhibiting the inhibitors: targeting anti-apoptotic proteins in cancer and therapy resistance. Drug Resist Updat 52:100712. https://doi.org/10.1016/j.drup.2020.100712

    Article  Google Scholar 

  22. Nikolaou M, Pavlopoulou A, Georgakilas AG, Kyrodimos E (2018) The challenge of drug resistance in cancer treatment: a current overview. Clin Exp Metastasis 35:309–318. https://doi.org/10.1007/s10585-018-9903-0

    Article  CAS  Google Scholar 

  23. Zhou B, Gao Y, Zhang P, Chu Q (2021) Acquired resistance to immune checkpoint blockades: the underlying mechanisms and potential strategies. Front Immunol 12:693609. https://doi.org/10.3389/fimmu.2021.693609

    Article  CAS  Google Scholar 

  24. Huang T, Song C, Zheng L, Xia L, Li Y, Zhou Y (2019) The roles of extracellular vesicles in gastric cancer development, microenvironment, anti-cancer drug resistance, and therapy. Mol Cancer 18:62. https://doi.org/10.1186/s12943-019-0967-5

    Article  Google Scholar 

  25. Vasan N, Baselga J, Hyman DM (2019) A view on drug resistance in cancer. Nature 575:299–309. https://doi.org/10.1038/s41586-019-1730-1

    Article  CAS  Google Scholar 

  26. Freimund AE, Beach JA, Christie EL, Bowtell DDL (2018) Mechanisms of drug resistance in high-grade serous ovarian cancer. Hematol Oncol Clin North Am 32:983–996. https://doi.org/10.1016/j.hoc.2018.07.007

    Article  Google Scholar 

  27. Maacha S, Bhat AA, Jimenez L, Raza A, Haris M, Uddin S, Grivel JC (2019) Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anti-cancer drug resistance. Mol Cancer 18:55. https://doi.org/10.1186/s12943-019-0965-7

    Article  Google Scholar 

  28. Rizzuti IF, Mascheroni P, Arcucci S, Ben-Mériem Z, Prunet A, Barentin C, Rivière C, Delanoë-Ayari H, Hatzikirou H, Guillermet-Guibert J, Delarue M (2020) Mechanical control of cell proliferation increases resistance to chemotherapeutic agents. Phys Rev Lett 125:128103. https://doi.org/10.1103/PhysRevLett.125.128103

    Article  CAS  Google Scholar 

  29. Fu J, Li T, Yang Y, Jiang L, Wang W, Fu L, Zhu Y, Hao Y (2021) Activatable nanomedicine for overcoming hypoxia-induced resistance to chemotherapy and inhibiting tumor growth by inducing collaborative apoptosis and ferroptosis in solid tumors. Biomaterials 268:120537. https://doi.org/10.1016/j.biomaterials.2020.120537

    Article  CAS  Google Scholar 

  30. Tang T, Yang ZY, Wang D, Yang XY, Wang J, Li L, Wen Q, Gao L, Bian XW, Yu SC (2020) The role of lysosomes in cancer development and progression. Cell Biosci 10:131. https://doi.org/10.1186/s13578-020-00489-x

    Article  Google Scholar 

  31. Grasso C, Jansen G, Giovannetti E (2017) Drug resistance in pancreatic cancer: Impact of altered energy metabolism. Crit Rev Oncol Hematol 114:139–152. https://doi.org/10.1016/j.critrevonc.2017.03.026

    Article  Google Scholar 

  32. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839. https://doi.org/10.1016/s0092-8674(00)81410-5

    Article  CAS  Google Scholar 

  33. Fernandez-Marcos PJ, Auwerx J (2011) Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr 93:884s-s890. https://doi.org/10.3945/ajcn.110.001917

    Article  CAS  Google Scholar 

  34. Chambers JM, Addiego A, Flores-Mireles AL, Wingert RA (2020) Ppargc1a controls ciliated cell development by regulating prostaglandin biosynthesis. Cell Rep 33:108370. https://doi.org/10.1016/j.celrep.2020.108370

    Article  CAS  Google Scholar 

  35. Andrzejewski S, Klimcakova E, Johnson RM, Tabariès S, Annis MG, McGuirk S, Northey JJ, Chénard V, Sriram U, Papadopoli DJ, Siegel PM, St-Pierre J (2017) PGC-1α promotes breast cancer metastasis and confers bioenergetic flexibility against metabolic drugs. Cell Metab 26:778-787.e5. https://doi.org/10.1016/j.cmet.2017.09.006

    Article  CAS  Google Scholar 

  36. Misu H, Takayama H, Saito Y, Mita Y, Kikuchi A, Ishii KA, Chikamoto K, Kanamori T, Tajima N, Lan F, Takeshita Y, Honda M, Tanaka M, Kato S, Matsuyama N, Yoshioka Y, Iwayama K, Tokuyama K, Akazawa N, Maeda S, Takekoshi K, Matsugo S, Noguchi N, Kaneko S, Takamura T (2017) Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle. Nat Med 23:508–516. https://doi.org/10.1038/nm.4295

    Article  CAS  Google Scholar 

  37. Park JH, Pyun WY, Park HW (2020) Cancer metabolism: phenotype. Signal Therap Targets Cells. https://doi.org/10.3390/cells9102308

    Article  Google Scholar 

  38. Missiroli S, Perrone M, Genovese I, Pinton P, Giorgi C (2020) Cancer metabolism and mitochondria: finding novel mechanisms to fight tumours. EBioMedicine 59:102943. https://doi.org/10.1016/j.ebiom.2020.102943

    Article  CAS  Google Scholar 

  39. Pascale RM, Calvisi DF, Simile MM, Feo CF, Feo F (2020) The Warburg effect 97 years after its discovery. Cancers (Basel). https://doi.org/10.3390/cancers12102819

    Article  Google Scholar 

  40. Liberti MV, Locasale JW (2016) The Warburg effect: How does it benefit cancer cells? Trends Biochem Sci 41:211–218. https://doi.org/10.1016/j.tibs.2015.12.001

    Article  CAS  Google Scholar 

  41. Golias T, Kery M, Radenkovic S, Papandreou I (2019) Microenvironmental control of glucose metabolism in tumors by regulation of pyruvate dehydrogenase. Int J Cancer 144:674–686. https://doi.org/10.1002/ijc.31812

    Article  CAS  Google Scholar 

  42. Goodpaster BH, Sparks LM (2017) Metabolic flexibility in health and disease. Cell Metab 25:1027–1036. https://doi.org/10.1016/j.cmet.2017.04.015

    Article  CAS  Google Scholar 

  43. Schwartz L, Seyfried T, Alfarouk KO, Da Veiga MJ, Fais S (2017) Out of Warburg effect: an effective cancer treatment targeting the tumor specific metabolism and dysregulated pH. Semin Cancer Biol 43:134–138. https://doi.org/10.1016/j.semcancer.2017.01.005

    Article  CAS  Google Scholar 

  44. Adeva-Andany MM, Pérez-Felpete N, Fernández-Fernández C, Donapetry-García C, Pazos-García C (2016) Liver glucose metabolism in humans. Biosci Rep. https://doi.org/10.1042/bsr20160385

  45. Li Z, Tang X, Luo Y, Chen B, Zhou C, Wu X, Tang Z, Qi X, Cao G, Hao J, Liu Z, Wang Q, Yin Z, Yang H (2019) NK007 helps in mitigating paclitaxel resistance through p38MAPK activation and HK2 degradation in ovarian cancer. J Cell Physiol. https://doi.org/10.1002/jcp.28278

    Article  Google Scholar 

  46. Chen L, Tang Z, Wang X, Ma H, Shan D, Cui S (2017) PKM2 aggravates palmitate-induced insulin resistance in HepG2 cells via STAT3 pathway. Biochem Biophys Res Commun 492:109–115. https://doi.org/10.1016/j.bbrc.2017.08.025

    Article  CAS  Google Scholar 

  47. Wang D, Zhao C, Xu F, Zhang A, Jin M, Zhang K, Liu L, Hua Q, Zhao J, Liu J, Yang H, Huang G (2021) Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2. Theranostics 11:2860–2875. https://doi.org/10.7150/thno.51797

    Article  CAS  Google Scholar 

  48. Vaupel P, Multhoff G (2021) Revisiting the Warburg effect: historical dogma versus current understanding. J Physiol 599:1745–1757. https://doi.org/10.1113/jp278810

    Article  CAS  Google Scholar 

  49. Olorundare O, Adeneye A, Akinsola A, Soyemi S, Mgbehoma A, Okoye I, Ntambi JM, Mukhtar H (2020) African vegetables (Clerodendrum volibile leaf and irvingia gabonensis seed extracts) effectively mitigate trastuzumab-induced cardiotoxicity in wistar rats. Oxid Med Cell Longev 2020:9535426. https://doi.org/10.1155/2020/9535426

    Article  CAS  Google Scholar 

  50. Vidri RJ, Fitzgerald TL (2020) GSK-3: an important kinase in colon and pancreatic cancers. Biochim Biophys Acta Mol Cell Res 1867:118626. https://doi.org/10.1016/j.bbamcr.2019.118626

    Article  CAS  Google Scholar 

  51. Kazi A, Xiang S, Yang H, Delitto D, Trevino J, Jiang RHY, Ayaz M, Lawrence HR, Kennedy P, Sebti SM (2018) GSK3 suppression upregulates β-catenin and c-Myc to abrogate KRas-dependent tumors. Nat Commun 9:5154. https://doi.org/10.1038/s41467-018-07644-6

    Article  CAS  Google Scholar 

  52. Li W, Wong CC, Zhang X, Kang W, Nakatsu G, Zhao Q, Chen H, Go MYY, Chiu PWY, Wang X, Ji J, Li X, Cai Z, Ng EKW, Yu J (2018) CAB39L elicited an anti-Warburg effect via a LKB1-AMPK-PGC1α axis to inhibit gastric tumorigenesis. Oncogene 37:6383–6398. https://doi.org/10.1038/s41388-018-0402-1

    Article  CAS  Google Scholar 

  53. Liu B, Jin J, Zhang Z, Zuo L, Jiang M, Xie C (2019) Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1α signaling pathway. Biochem Cell Biol 97:397–405. https://doi.org/10.1139/bcb-2018-0310

    Article  CAS  Google Scholar 

  54. Icard P, Shulman S, Farhat D, Steyaert JM, Alifano M, Lincet H (2018) How the Warburg effect supports aggressiveness and drug resistance of cancer cells? Drug Resist Updat 38:1–11. https://doi.org/10.1016/j.drup.2018.03.001

    Article  Google Scholar 

  55. Woolbright BL, Rajendran G, Harris RA, Taylor JA 3rd (2019) Metabolic flexibility in cancer: targeting the pyruvate dehydrogenase kinase: pyruvate dehydrogenase axis. Mol Cancer Ther 18:1673–1681. https://doi.org/10.1158/1535-7163.Mct-19-0079

    Article  CAS  Google Scholar 

  56. Summermatter S, Santos G, Pérez-Schindler J, Handschin C (2013) Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A. Proc Natl Acad Sci USA 110:8738–8743. https://doi.org/10.1073/pnas.1212976110

    Article  Google Scholar 

  57. Oyewole AO, Birch-Machin MA (2015) Mitochondria-targeted antioxidants. Faseb j 29:4766–4771. https://doi.org/10.1096/fj.15-275404

    Article  CAS  Google Scholar 

  58. Sorrentino V, Menzies KJ, Auwerx J (2018) Repairing mitochondrial dysfunction in disease. Annu Rev Pharmacol Toxicol 58:353–389. https://doi.org/10.1146/annurev-pharmtox-010716-104908

    Article  CAS  Google Scholar 

  59. Luo Y, Ma J, Lu W (2020) The significance of mitochondrial dysfunction in cancer. Int J Mol Sci. https://doi.org/10.3390/ijms21165598

    Article  Google Scholar 

  60. Rodríguez-Hernández MA, de la Cruz-Ojeda P, López-Grueso MJ, Navarro-Villarán E, Requejo-Aguilar R, Castejón-Vega B, Negrete M, Gallego P, Vega-Ochoa Á, Victor VM, Cordero MD, Del Campo JA, Bárcena JA, Padilla CA, Muntané J (2020) Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer. Redox Biol 36:101510. https://doi.org/10.1016/j.redox.2020.101510

    Article  CAS  Google Scholar 

  61. Molnar MJ, Kovacs GG (2017) Mitochondrial diseases. Handb Clin Neurol 145:147–155. https://doi.org/10.1016/b978-0-12-802395-2.00010-9

    Article  Google Scholar 

  62. Wu L, Liu X, Cao KX, Ni ZH, Li WD, Chen ZP (2018) Synergistic antitumor effects of rhein and doxorubicin in hepatocellular carcinoma cells. J Cell Biochem. https://doi.org/10.1002/jcb.27514

    Article  Google Scholar 

  63. Cocetta V, Ragazzi E, Montopoli M (2019) Mitochondrial involvement in cisplatin resistance. Int J Mol Sci. https://doi.org/10.3390/ijms20143384

    Article  Google Scholar 

  64. Narita N, Ito Y, Takabayashi T, Okamoto M, Imoto Y, Ogi K, Tokunaga T, Matsumoto H, Fujieda S (2018) Suppression of SESN1 reduces cisplatin and hyperthermia resistance through increasing reactive oxygen species (ROS) in human maxillary cancer cells. Int J Hyperthermia 35:269–278. https://doi.org/10.1080/02656736.2018.1496282

    Article  CAS  Google Scholar 

  65. Han Y, Kim B, Cho U, Park IS, Kim SI, Dhanasekaran DN, Tsang BK, Song YS (2019) Mitochondrial fission causes cisplatin resistance under hypoxic conditions via ROS in ovarian cancer cells. Oncogene 38:7089–7105. https://doi.org/10.1038/s41388-019-0949-5

    Article  CAS  Google Scholar 

  66. Yang Y, Liu PY, Bao W, Chen SJ, Wu FS, Zhu PY (2020) Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway. BMC Cancer 20:28. https://doi.org/10.1186/s12885-019-6491-6

    Article  CAS  Google Scholar 

  67. Srinivasan S, Guha M, Kashina A, Avadhani NG (2017) Mitochondrial dysfunction and mitochondrial dynamics-the cancer connection. Biochim Biophys Acta Bioenerg 1858:602–614. https://doi.org/10.1016/j.bbabio.2017.01.004

    Article  CAS  Google Scholar 

  68. Lee H, Yoon Y (2018) Mitochondrial membrane dynamics-functional positioning of OPA1. Antioxidants (Basel). https://doi.org/10.3390/antiox7120186

    Article  Google Scholar 

  69. Jourdain A, Martinou JC (2009) Mitochondrial outer-membrane permeabilization and remodelling in apoptosis. Int J Biochem Cell Biol 41:1884–1889. https://doi.org/10.1016/j.biocel.2009.05.001

    Article  CAS  Google Scholar 

  70. Chan DC (2020) Mitochondrial dynamics and its involvement in disease. Annu Rev Pathol 15:235–259. https://doi.org/10.1146/annurev-pathmechdis-012419-032711

    Article  CAS  Google Scholar 

  71. Baker N, Patel J, Khacho M (2019) Linking mitochondrial dynamics, cristae remodeling and supercomplex formation: How mitochondrial structure can regulate bioenergetics. Mitochondrion 49:259–268. https://doi.org/10.1016/j.mito.2019.06.003

    Article  CAS  Google Scholar 

  72. Yu W, Zha W, Ren J (2018) Exendin-4 and liraglutide attenuate glucose toxicity-induced cardiac injury through mTOR/ULK1-dependent autophagy. Oxid Med Cell Longev 2018:5396806. https://doi.org/10.1155/2018/5396806

    Article  CAS  Google Scholar 

  73. Shenouda SM, Widlansky ME, Chen K, Xu G, Holbrook M, Tabit CE, Hamburg NM, Frame AA, Caiano TL, Kluge MA, Duess MA, Levit A, Kim B, Hartman ML, Joseph L, Shirihai OS, Vita JA (2011) Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus. Circulation 124:444–453. https://doi.org/10.1161/circulationaha.110.014506

    Article  CAS  Google Scholar 

  74. Peng K, Yang L, Wang J, Ye F, Dan G, Zhao Y, Cai Y, Cui Z, Ao L, Liu J, Zou Z, Sai Y, Cao J (2017) The interaction of mitochondrial biogenesis and fission/fusion mediated by PGC-1α regulates rotenone-induced dopaminergic neurotoxicity. Mol Neurobiol 54:3783–3797. https://doi.org/10.1007/s12035-016-9944-9

    Article  CAS  Google Scholar 

  75. Li J, Ke W, Zhou Q, Wu Y, Luo H, Zhou H, Yang B, Guo Y, Zheng Q, Zhang Y (2014) Tumour necrosis factor-α promotes liver ischaemia-reperfusion injury through the PGC-1α/Mfn2 pathway. J Cell Mol Med 18:1863–1873. https://doi.org/10.1111/jcmm.12320

    Article  CAS  Google Scholar 

  76. Izzo A, Nitti M, Mollo N, Paladino S, Procaccini C, Faicchia D, Calì G, Genesio R, Bonfiglio F, Cicatiello R, Polishchuk E, Polishchuk R, Pinton P, Matarese G, Conti A, Nitsch L (2017) Metformin restores the mitochondrial network and reverses mitochondrial dysfunction in down syndrome cells. Hum Mol Genet 26:1056–1069. https://doi.org/10.1093/hmg/ddx016

    Article  CAS  Google Scholar 

  77. Agudelo LZ, Ferreira DMS, Dadvar S, Cervenka I, Ketscher L, Izadi M, Zhengye L, Furrer R, Handschin C, Venckunas T, Brazaitis M, Kamandulis S, Lanner JT, Ruas JL (2019) Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance. Nat Commun 10:2767. https://doi.org/10.1038/s41467-019-10712-0

    Article  CAS  Google Scholar 

  78. Zhang RN, Shen F, Pan Q, Cao HX, Chen GY, Fan JG (2021) PPARGC1A rs8192678 G>A polymorphism affects the severity of hepatic histological features and nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease. World J Gastroenterol 27:3863–3876. https://doi.org/10.3748/wjg.v27.i25.3863

    Article  CAS  Google Scholar 

  79. Gentric G, Kieffer Y, Mieulet V, Goundiam O, Bonneau C, Nemati F, Hurbain I, Raposo G, Popova T, Stern MH, Lallemand-Breitenbach V, Müller S, Cañeque T, Rodriguez R, Vincent-Salomon A, de Thé H, Rossignol R, Mechta-Grigoriou F (2019) PML-regulated mitochondrial metabolism enhances chemosensitivity in human ovarian cancers. Cell Metab 29:156-173.e10. https://doi.org/10.1016/j.cmet.2018.09.002

    Article  CAS  Google Scholar 

  80. Ding Y, Yang H, Wang Y, Chen J, Ji Z, Sun H (2017) Sirtuin 3 is required for osteogenic differentiation through maintenance of PGC-1ɑ-SOD2-mediated regulation of mitochondrial function. Int J Biol Sci 13:254–264. https://doi.org/10.7150/ijbs.17053

    Article  CAS  Google Scholar 

  81. Hasan-Olive MM, Lauritzen KH, Ali M, Rasmussen LJ, Storm-Mathisen J, Bergersen LH (2019) A ketogenic diet improves mitochondrial biogenesis and bioenergetics via the PGC1α-SIRT3-UCP2 Axis. Neurochem Res 44:22–37. https://doi.org/10.1007/s11064-018-2588-6

    Article  CAS  Google Scholar 

  82. Liao X, Zhang R, Lu Y, Prosdocimo DA, Sangwung P, Zhang L, Zhou G, Anand P, Lai L, Leone TC, Fujioka H, Ye F, Rosca MG, Hoppel CL, Schulze PC, Abel ED, Stamler JS, Kelly DP, Jain MK (2015) Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis. J Clin Invest 125:3461–3476. https://doi.org/10.1172/jci79964

    Article  Google Scholar 

  83. Liu H, Zhu S, Han W, Cai Y, Liu C (2021) DMEP induces mitochondrial damage regulated by inhibiting Nrf2 and SIRT1/PGC-1α signaling pathways in HepG2 cells. Ecotoxicol Environ Saf 221:112449. https://doi.org/10.1016/j.ecoenv.2021.112449

    Article  CAS  Google Scholar 

  84. Cordani M, Butera G, Dando I, Torrens-Mas M, Butturini E, Pacchiana R, Oppici E, Cavallini C, Gasperini S, Tamassia N, Nadal-Serrano M, Coan M, Rossi D, Gaidano G, Caraglia M, Mariotto S, Spizzo R, Roca P, Oliver J, Scupoli MT, Donadelli M (2018) Mutant p53 blocks SESN1/AMPK/PGC-1α/UCP2 axis increasing mitochondrial O(2-)·production in cancer cells. Br J Cancer 119:994–1008. https://doi.org/10.1038/s41416-018-0288-2

    Article  CAS  Google Scholar 

  85. LeBleu VS, O’Connell JT, Gonzalez Herrera KN, Wikman H, Pantel K, Haigis MC, de Carvalho FM, Damascena A, Domingos Chinen LT, Rocha RM, Asara JM, Kalluri R (2014) PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol 16(992–1003):1–15. https://doi.org/10.1038/ncb3039

    Article  CAS  Google Scholar 

  86. Wang S, Wan T, Ye M, Qiu Y, Pei L, Jiang R, Pang N, Huang Y, Liang B, Ling W, Lin X, Zhang Z, Yang L (2018) Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway. Redox Biol 17:89–98. https://doi.org/10.1016/j.redox.2018.04.006

    Article  CAS  Google Scholar 

  87. Qian X, Li X, Shi Z, Bai X, Xia Y, Zheng Y, Xu D, Chen F, You Y, Fang J, Hu Z, Zhou Q, Lu Z (2019) KDM3A senses oxygen availability to regulate PGC-1α-mediated mitochondrial biogenesis. Mol Cell 76:885-895.e7. https://doi.org/10.1016/j.molcel.2019.09.019

    Article  CAS  Google Scholar 

  88. Salazar G, Cullen A, Huang J, Zhao Y, Serino A, Hilenski L, Patrushev N, Forouzandeh F, Hwang HS (2020) SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. Autophagy 16:1092–1110. https://doi.org/10.1080/15548627.2019.1659612

    Article  CAS  Google Scholar 

  89. Vainshtein A, Tryon LD, Pauly M, Hood DA (2015) Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am J Physiol Cell Physiol 308:C710–C719. https://doi.org/10.1152/ajpcell.00380.2014

    Article  CAS  Google Scholar 

  90. Cherry AD, Piantadosi CA (2015) Regulation of mitochondrial biogenesis and its intersection with inflammatory responses. Antioxid Redox Signal 22:965–976. https://doi.org/10.1089/ars.2014.6200

    Article  CAS  Google Scholar 

  91. Schmitt R, Schindler G, Gutzeit B (1986) Biloma in the subhepatic space and omental bursa after revision of the choledochus. Rofo 145:601–603. https://doi.org/10.1055/s-2008-1048997

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank all the reviewers who participated in the review and MJEditor (www.mjeditor.com) for its linguistic assistance during the preparation of this manuscript.

Funding

This study funded by Henan Science and Technology Key Project (222102310612).

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Authors and Affiliations

  1. Department of Thyroid and Neck, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, China

    Yanqing Li, Hu Hei, Songtao Zhang, Wenbo Gong & Jianwu Qin

  2. Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, People’s Republic of China

    Yann Liu

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  1. Yanqing Li
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  2. Hu Hei
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Contributions

YL and JQ contributed to the conception and design of the study. YL and HH contributed to the drafting or revision of study with important knowledge contents. SZ and YL designed and depicted the diagram. WG, YL and JQ finally approved the forthcoming edition. All authors agree to be responsible for all aspects of the project and ensure that problems related to the accuracy or completeness of any part of the project are properly investigated and solved.

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Correspondence to Yann Liu or Jianwu Qin.

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Li, Y., Hei, H., Zhang, S. et al. PGC-1α participates in tumor chemoresistance by regulating glucose metabolism and mitochondrial function. Mol Cell Biochem 478, 47–57 (2023). https://doi.org/10.1007/s11010-022-04477-2

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