본문 바로가기
KERD
논문KCI 등재

Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal Ca2+ release

Lee Myung-Shik|Oh Soo-Jin|Park Kihyoun|Sonn Seong Keun|Oh Goo Taeg
생화학분자생물학회 (Korean Society Of Biochemistry And Molecular Biology)|2023.12|Experimental and Molecular Medicine|제55권 |pp. 1922-1932|DOI 10.1038/s12276-023-01055-4

0

조회

0

다운로드

0

인용

0

참고문헌

주제분류생화학

초록

Mitophagy is an excellent example of selective autophagy that eliminates damaged or dysfunctional mitochondria, and it is crucial for the maintenance of mitochondrial integrity and function. The critical roles of autophagy in pancreatic β-cell structure and function have been clearly shown. Furthermore, morphological abnormalities and decreased function of mitochondria have been observed in autophagy-deficient β-cells, suggesting the importance of β-cell mitophagy. However, the role of authentic mitophagy in β-cell function has not been clearly demonstrated, as mice with pancreatic β-cell-specific disruption of Parkin, one of the most important players in mitophagy, did not exhibit apparent abnormalities in β-cell function or glucose homeostasis. Instead, the role of mitophagy in pancreatic β-cells has been investigated using β-cell-specific Tfeb-knockout mice (TfebΔβ-cell mice); Tfeb is a master regulator of lysosomal biogenesis or autophagy gene expression and participates in mitophagy. TfebΔβ-cell mice were unable to adaptively increase mitophagy or mitochondrial complex activity in response to high-fat diet (HFD)-induced metabolic stress. Consequently, TfebΔβ-cell mice exhibited impaired β-cell responses and further exacerbated metabolic deterioration after HFD feeding. TFEB was activated by mitochondrial or metabolic stress-induced lysosomal Ca2+ release, which led to calcineurin activation and mitophagy. After lysosomal Ca2+ release, depleted lysosomal Ca2+ stores were replenished by ER Ca2+ through ER→lysosomal Ca2+ refilling, which supplemented the low lysosomal Ca2+ capacity. The importance of mitophagy in β-cell function was also demonstrated in mice that developed β-cell dysfunction and glucose intolerance after treatment with a calcineurin inhibitor that hampered TFEB activation and mitophagy.

Abstract

Mitophagy is an excellent example of selective autophagy that eliminates damaged or dysfunctional mitochondria, and it is crucial for the maintenance of mitochondrial integrity and function. The critical roles of autophagy in pancreatic β-cell structure and function have been clearly shown. Furthermore, morphological abnormalities and decreased function of mitochondria have been observed in autophagy-deficient β-cells, suggesting the importance of β-cell mitophagy. However, the role of authentic mitophagy in β-cell function has not been clearly demonstrated, as mice with pancreatic β-cell-specific disruption of Parkin, one of the most important players in mitophagy, did not exhibit apparent abnormalities in β-cell function or glucose homeostasis. Instead, the role of mitophagy in pancreatic β-cells has been investigated using β-cell-specific Tfeb-knockout mice (TfebΔβ-cell mice); Tfeb is a master regulator of lysosomal biogenesis or autophagy gene expression and participates in mitophagy. TfebΔβ-cell mice were unable to adaptively increase mitophagy or mitochondrial complex activity in response to high-fat diet (HFD)-induced metabolic stress. Consequently, TfebΔβ-cell mice exhibited impaired β-cell responses and further exacerbated metabolic deterioration after HFD feeding. TFEB was activated by mitochondrial or metabolic stress-induced lysosomal Ca2+ release, which led to calcineurin activation and mitophagy. After lysosomal Ca2+ release, depleted lysosomal Ca2+ stores were replenished by ER Ca2+ through ER→lysosomal Ca2+ refilling, which supplemented the low lysosomal Ca2+ capacity. The importance of mitophagy in β-cell function was also demonstrated in mice that developed β-cell dysfunction and glucose intolerance after treatment with a calcineurin inhibitor that hampered TFEB activation and mitophagy.

참고문헌 (107)

  1. Berger, C., "Glucose transporters in pancreatic islets", Pflug. Arch, 472, pp.1249~1272 (2022)
  2. Lee, M.-S., "Role of mitochondrial function in cell death and metabolism", Front. Biosci, 21, pp.1233~1244 (2016)
  3. Jung, H. S., "Loss of autophagy diminishes pancreatic b-cell mass and function with resultant hyperglycemia", Cell Metab, 8, pp.318~324 (2008)
  4. Ebato, C., "Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet", Cell Metab, 8, pp.325~332 (2008)
  5. Corsa, C. A. S., "The E3 ubiquitin ligase Parkin is dispensable for metabolic homeostasis in murine pancreatic β cells and adipocytes", J. Biol. Chem, 294, pp.7296~7307 (2019)
  6. Medina, D. L., "Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB", Nat. Cell Biol, 17, pp.288~299 (2015)
  7. Mizushima, N., "Autophagy : renovation of cells and tissues", Cell, 147, pp.728~741 (2011)
  8. Nieto-Torres, J. L., "Beyond autophagy : the expanding roles of ATG8 proteins", Trends Biochem. Sci, 46, pp.673~686 (2021)
  9. Lu, G., "Autophagy in health and disease : from molecular mechanisms to therapeutic target", MedComm, 3, pp.e150~ (2022)
  10. Bohr, V. A., "DNA damage, mutation and fine structure DNA repair in aging", Mutat. Res, 338, pp.25~34 (1995)
  11. Jin, S. M., "Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL", J. Cell Biol, 191, pp.933~942 (2010)
  12. Pickrell, A. M, "The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease", Neuron, 85, pp.257~273 (2015)
  13. Koyano, F., "Ubiquitin is phosphorylated by PINK1 to activate parkin", Nature, 10, pp.162~166 (2014)
  14. Heo, J. -M., "The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN", NDP52recruitment and TBK1 activation to promote mitophagy, 2015, pp.60, 7~20
  15. Moore, A. S., "Dynamic recruitment and activation of ALSassociated TBK1 with its target optineurin are required for efficient mitophagy", Proc. Natl Acad. Sci. USA, 113, pp.E3349~E3358 (2016)
  16. Vargas, J. N. S., "Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy", Mol. Cell, 74, pp.347~362 (2019)
  17. Wu, H., "Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome", Autophagy, 15, pp.1882~1898 (2019)
  18. Zhang, J., "Role of BNIP3 and NIX in cell death, autophagy, and mitophagy", Cell Death Differ, 16, pp.939~946 (2009)
  19. Wei, Y., "Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor", Cell, 168, pp.224~238 (2017)
  20. Abudu, Y. P., "SAMM50 acts with p62 in piecemeal basal-and OXPHOSinduced mitophagy of SAM and MICOS components", J. Cell Biol, 220, pp.c202009092~ (2021)
  21. Le Guerroué, F., "Autophagosomal content profiling reveals an LC3Cdependent piecemeal mitophagy pathway", Mol. Cell, 68, pp.786~796 (2017)
  22. Lemasters, J. J., "Variants of mitochondrial autophagy : types 1 and 2 mitophagy and micromitophagy(Type 3)", Redox Biol, 2, pp.749~754 (2014)
  23. Chu, C. T., "Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells", Nat. Cell Biol, 15, pp.1197~1205 (2013)
  24. Nguyen, T. N., "Atg8 family LC3", GABARAP proteins are crucial for autophagosome-lysosome fusion but not autophagosome formation during PINK1, J. Cell Biol, pp.2016, 215[DOI]
  25. Nishida, Y., "Discovery of Atg5", Atg7-independent alternative macroautophagy, 2009, pp.461, 654~658
  26. Burman, J. L., "Mitochondrial fission facilitates the selective mitophagy of protein aggregates", J. Cell Biol, 216, pp.3231~3247 (2017)
  27. Kleele, T., "Distinct fission signatures predict mitochondrial degradation or biogenesis", Nature, 593, pp.435~439 (2021)
  28. Settembre, C., "TFEB controls cellular lipid metabolism through a starvationinduced autoregulatory loop", Nat. Cell Biol, 15, pp.647~658 (2013)
  29. Nezich, C. L., "MiT", TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5, 2015, pp.210, 435~450
  30. Zhang, X., "MCOLN1 is a ROS sensor in lysosomes that regulates autophagy", Nat. Commun, 7, pp.12109~ (2016)
  31. Zhang, X., "Lysosome calcium in ROS regulation of autophagy", Autophagy, 12, pp.1954~1955 (2016)
  32. Wang, W., "Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation", Proc. Natl Acad. Sci. USA, 112, pp.E1373~E1381 (2015)
  33. Penny, C. J., "A computational model of lysosome-ER Ca2+ microdomains", J. Cell Sci, 127, pp.2934~2943 (2014)
  34. Goodwin, J. M., "GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis", Sci. Adv, 7, pp.eabj2485~ (2021)
  35. Napolitano, G., "A substrate-specific mTORC1 pathway underlies Birt-Hogg-Dubé syndrome", Nature, 585, pp.597~602 (2020)
  36. Deretic, V., "A guide to membrane atg8ylation and autophagy with reflections on immunity", J. Cell Biol, 221, pp.e202203083~ (2022)
  37. Kim, K. H., "Autophagy-a key player in cellular and body metabolism", Nat. Rev. Endocrinol, 10, pp.322~337 (2014)
  38. Park, K., "Current status of autophagy enhancers in metabolic disorders and other diseases", Front. Cell Dev. Biol, 10, pp.1~21 (2022)
  39. Bugliani, M., "Modulation of autophagy influences the function and survival of human pancreatic beta cells under endoplasmic reticulum stress conditions and in type 2 diabetes", Front. Endocrinol, 10, pp.52~ (2019)
  40. Choi, S. E., "Protective role of autophagy in palmitate-induced INS-1 beta cell death", Endocrinology, 150, pp.126~134 (2009)
  41. Kim, J., "An autophagy enhancer ameliorates diabetes of human IAPPtransgenic mice through clearance of amyloidogenic oligomer", Nat. Commun, 12, pp.183~ (2021)
  42. King, B. C., "Complement component C3 Is highly expressed in human pancreatic islets and prevents β cell death via ATG16L1 interaction and autophagy regulation", Cell Metab, 29, pp.1~9 (2018)
  43. Hoshino, A., "Inhibition of p53 preserves Parkin-mediated mitophagy and pancreatic β-cell function in diabetes", Proc. Natl Acad. Sci. USA, 111, pp.3116~3121 (2014)
  44. Quan, W., "Autophagy deficiency in beta cells leads to compromised unfolded protein response and progression from obesity to diabetes in mice", Diabetologia, 55, pp.392~403 (2012)
  45. Lim, Y. -M., "Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes", Nat. Commun, 5, pp.4934~ (2014)
  46. Ji, J., "Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in β-cells", J. Cell. Mol. Med, 23, pp.2890~2900 (2019)
  47. Lee, Y. H., "β-cell autophagy: Mechanism and role in β-cell dysfunction", Mol. Metab, 27S, pp.92~103 (2019)
  48. Liu, L., "Mitochondrial outer-membrane protein FUNDC1 mediates hypoxiainduced mitophagy in mammalian cells", Nat. Cell Biol, 14, pp.177~185 (2012)
  49. Kim, K. Y., "Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells", J. Clin. Invest, 121, pp.3701~3712 (2011)
  50. Lu, X., "Mitophagy controls beige adipocyte maintenance through a Parkindependent and UCP1-independent mechanism", Sci. Signal, 11, pp.eaap8526~ (2018)
  51. Deas, E., "PINK1 deficiency in β-cells increases basal insulin secretion and improves glucose tolerance in mice", Open Biol, 4, pp.144051~ (2014)
  52. McWilliams, T. G., "Basal mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand", Cell Metab, 27, pp.439~449 (2018)
  53. Ko, M. S., "Mitophagy deficiency increases NLRP3 to induce brown fat dysfunction in mice", Autophagy, 17, pp.1205~1221 (2021)
  54. Howson, J. M., "Genetic analysis of adult-onset autoimmune diabetes", Diabetes, 60, pp.2645~2653 (2011)
  55. Soleimanpour, S. A., "The diabetes susceptibility gene Clec16a regulates mitophagy", Cell, 157, pp.1577~1590 (2014)
  56. Pearson, G., "Clec16a, Nrdp1, and USP8 form a ubiquitin-dependent tripartite complex that regulates β-cell mitophagy", Diabetes, 67, pp.265~277 (2018)
  57. Soleimanpour, S. A., "Diabetes susceptibility genes Pdx1 and Clec16a function in a pathway regulating mitophagy in β-cells", Diabetes, 64, pp.3475~3484 (2015)
  58. Sidarala, V., "Mitophagy protects β cells from inflammatory damage in diabetes", JCI Insignt, 5, pp.e141138~ (2020)
  59. Gingerich, M. A., "An intrinsically disordered protein region encoded by the human disease gene CLEC16A regulates mitophagy", Autophagy, 30, pp.1~19 (2022)
  60. Smits, D. S., "CLEC16A interacts with retromer and TRIM27, and its loss impairs endosomal trafficking and neurodevelopment", Hum. Genet, 142, pp.379~397 (2022)
  61. Dunkerley, K. M., "Distinct phosphorylation signals drive acceptor versus free ubiquitin chain targeting by parkin", Biochem. J, 479, pp.751~766 (2022)
  62. Wang, X., "The mechanism of Ca2+ -dependent regulation of kinesin-mediated mitochondrial motility", Cell, 136, pp.163~174 (2009)
  63. Chen, L., "Inhibition of Miro1 disturbs mitophagy and pancreatic β-cell function interfering insulin release via IRS-Akt-Foxo1 in diabetes", Oncotarget, 8, pp.90693~90705 (2017)
  64. Litonin, D., "Human mitochondrial transcription revisited : only TFAM and TFB2M are required for transcription of the mitochondrial genes in vitro", J. Biol. Chem, 285, pp.18129~18133 (2010)
  65. Nicholas, L. M., "Mitochondrial transcription factor B2 is essential for mitochondrial and cellular function in pancreatic β-cells", Mol. Metab, 6, pp.651~663 (2017)
  66. Close, A. -F., "Disruption of betacell mitochondrial networks by the orphan nuclear receptor Nor1", Nr4a3, 2020, pp.9, 168~
  67. Kusminski, C. M., "MitoNEET-Parkin effects in pancreatic α-and β-cells, cellular survival, and intrainsular cross talk", Diabetes, 65, pp.1534~1555 (2016)
  68. Georgakopoulos, N. D., "The pharmacological regulation of cellular mitophagy", Nat. Chem. Biol, 13, pp.136~146 (2017)
  69. Katayama, H., "A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery", Chem. Biol, 18, pp.1042~1052 (2011)
  70. Park, K., "Essential role of lysosomal Ca2+-mediated TFEB activation in mitophagy and functional adaptation of pancreatic ♌-cells to metabolic stress", Nat. Commun, 13, pp.1300~ (2022)
  71. Coll, T., "Oleate reverses palmitate-induced insulin resistance and inflammation in skeletal muscle cells", J. Biol. Chem, 283, pp.11107~11116 (2008)
  72. Karaskov, E., "Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic b-cell apoptosis", Endocrinology, 147, pp.3398~3407 (2006)
  73. Xu, S., "Palmitate induces ER calcium depletion and apoptosis in mouse podocytes subsequent to mitochondrial oxidative stress", Cell Death Dis, 6, pp.e1976~ (2015)
  74. Nakamura, S., "Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria", J. Biol. Chem, 284, pp.14809~14818 (2009)
  75. Fang, E. F., "Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease", Nat. Neurosci, 22, pp.401~412 (2019)
  76. Aoyagi, K., "A new beta cell-specific mitophagy reporter mouse shows that metabolic stress leads to accumulation of dysfunctional mitochondria despite increased mitophagy", Diabetologia, 66, pp.147~162 (2023)
  77. Tong, M., "Mitophagy is essential for maintaining cardiac function during high fat diet-induced diabetic cardiomyopathy", Circ. Res, 125, pp.1360~1371 (2019)
  78. Sun, N., "Measuring In vivo mitophagy", Mol. Cell, 60, pp.685~696 (2015)
  79. Cereghetti, G. M., "Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria", Proc. Natl Acad. Sci. USA, 105, pp.15803~15808 (2008)
  80. Zummo, F. P., "Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF", EPAC-Ca 2+-PPP3, Autophagy, pp.2021, 18[DOI]
  81. Dumont, F. J., "FK506, an immunosuppressant targeting calcineurin function", Curr. Med. Chem, 7, pp.731~748 (2000)
  82. Jenssen, T., "Post-transplant diabetes mellitus in patients with solid organ transplants", Nat. Rev. Endocrinol, 15, pp.172~188 (2019)
  83. Samie, M., "A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis", Dev. Cell, 26, pp.511~524 (2013)
  84. Garrity, A. G., "The endoplasmic reticulum, not the pH gradient, drives calcium refilling of lysosomes", eLife, 5, pp.e15887~ (2016)
  85. Nozawa, T., "TBC1D9 regulates TBK1 activation through Ca 2+ signaling in selective autophagy", Nat. Commun, 11, pp.770~ (2020)
  86. Kilpatrick, B. S., "Direct mobilisation of lysosomal Ca2+ triggers complex Ca2+ signals", J. Cell Sci, 126, pp.60~66 (2013)
  87. Derler, I., "Molecular mechanisms of STIM", Orai communication, 2016, pp.310, C643~C662
  88. Jia, J., "Stress granules and mTOR are regulated by membrane atg8ylation during lysosomal damage", J. Cell Biol, 221, pp.e202207091~ (2022)
  89. Rocha, C., "Cardiac mitochondrial respiration following a low-carbohydrate, high-fat diet in apolipoprotein E-deficient mice", J. Physiol. Biochem, 75, pp.65~72 (2019)
  90. Yu, H. -T., "Oxidative damage of mitochondrial respiratory chain in different organs of a rat model of diet-induce obesity", Eur. J. Nutr, 57, pp.1957~1967 (2018)
  91. Koga, H., "Altered lipid content inhibits autophagic vesicular fusion", FASEB J, 24, pp.3052~3065 (2010)
  92. Lim, Y., "Palmitate reduces starvation-induced ER stress by inhibiting ER-phagy in hypothalamic cells", Mol. Brain, 14, pp.65~ (2021)
  93. Mansueto, G., "Transcription Factor EB controls metabolic flexibility during exercise", Cell Metab, 25, pp.182~196 (2015)
  94. Liu, H., "Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the autophagy-lysosome pathway", Autophagy, 13, pp.1952~1968 (2017)
  95. Lazarou, M., "The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy", Nature, 524, pp.309~314 (2015)
  96. Doronzo, G., "TFEB controls vascular development by regulating the proliferation of endothelial cells", EMBO J, 38, pp.e98250~ (2019)
  97. Rottner, A. K., "A genome-wide CRISPR screen identifies CALCOCO2 as a regulator of beta cell function influencing type 2 diabetes risk", Nat. Genet, 55, pp.54~65 (2023)
  98. Martina, J. A., "Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress", J. Biol. Chem, 293, pp.12525~12534 (2018)
  99. Rostaing, L., "Belatacept-versus cyclosporine-based immunosuppression in renal transplant recipients with pre-existing diabetes", Clin. J. Am. Soc. Nephrol, 6, pp.2696~2704 (2011)
  100. Ponticelli, C., "Old and new calcineurin inhibitors in lupus nephritis", J. Clin. Med, 10, pp.4832~ (2021)
  101. Chakkera, H. A., "Calcineurin inhibitors : pharmacologic mechanisms impacting both insulin resistance and insulin secretion leading to glucose dysregulation and diabetes mellitus", Clin. Pharmacol. Ther, 101, pp.114~120 (2017)
  102. Fuhrer, D. K., "Insulin release and suppression by tacrolimus, rapamycin and cyclosporin A are through regulation of the ATPsensitive potassium channel", Diabetes Obes. Metab, 3, pp.393~402 (2001)
  103. Okamoto, H., "Recent advances in the Okamoto model : the CD38-cyclic ADP-ribose signal system and the regenerating gene protein(Reg)-Reg receptor system in beta-cells", Diabetes, 51, pp.462~473 (2002)
  104. Park, K., "Impaired TFEB activation and mitophagy as a cause of PPP3", calcineurin inhibitor-induced pancreatic β-cell dysfunction, 2022, pp.19, 1444~1458
  105. Lim, H., "A novel autophagy enhancer as a therapeutic agent against metabolic syndrome and diabetes", Nat. Commun, 9, pp.1438~ (2018)
  106. Adie, S. K., "Tacrolimus time in therapeutic range and long-term outcomes in heart transplant recipients", Pharmacotherapy, 42, pp.106~111 (2021)
  107. Li, D. L., "Doxorubicin blocks cardiomyocyte autophagic flux by inhibiting lysosome acidification", Circulation, 133, pp.1668~1687 (2016)

관련 논문AI추천

Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicityNguyen Ha Thu, Park Kyu-Sang, Wiederkehr Andreas, Wollheim Claes B.생화학분자생물학회 · Experimental and Molecular Medicine2024 · 제56권 Emerging role of mitophagy in human diseases and physiology엄지현, 윤진호생화학분자생물학회 · BMB Reports2017 · 제50권 제6호Mitoribosome insufficiency in β cells is associated with type 2 diabetes-like islet failureChang Joon Young, Choi Heejung, Choi Min Jeong, Hong Hyun Jung, Joung Kyong Hye, Jo Yunju, Jun Sangmi, Kang Baeki E., Kang Seul Gi, Kang Yea Eun, Kim Hail, Kim Hyeongseok, Kim Hyun Jin, Kim Jung Tae, Kim Yong Kyung, Lee Chul-Ho, Lee Yujeong, Moon Joon Ho, Park Jae-Hyung, Park Kyu-Sang, Ro Hyun-Joo, Ryu Dongryeol, Shong Minho생화학분자생물학회 · Experimental and Molecular Medicine2022 · 제54권 Exploring mitophagy levels in Drosophila Malpighian tubules unveils the pivotal role of mitophagy in kidney function and diabetic kidney diseaseJung Hye Lim, Kim Jihun, Kim Young Yeon, Lee Hyi-Seung, Lee Jihoon, Lee Kang-Min, Lee Yeonjung, Yoo Eunhee, Yun Jeanho생화학분자생물학회 · Experimental and Molecular Medicine2025 · 제57권 SENP2 regulates mitochondrial function and insulin secretion in pancreatic β cells정성수, Lee Dong-Sup, Lee Ji Seon, Lee Seung-Ah, Moon Joon Ho, Nan Jinyan, Park Kyong Soo, Park Young Joo생화학분자생물학회 · Experimental and Molecular Medicine2022 · 제54권 Channel Function of TRPML1 Prompts Lipolysis in Mature Adipocytes김미성, 김민석대한구강생물학회 · International Journal of Oral Biology2018 · 제43권 제1호

이 간행물의 다른 논문 (225건)

Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics김성영, Han Yeaeunpp. 1-12Grave-to-cradle: human embryonic lineage tracing from the postmortem bodyKu Eu Jeong, Choi Seock Hwan, Choi Yujin Angelina, Oh Ji Wonpp. 13-21Chromatin and noncoding RNA-mediated mechanisms of gastric tumorigenesisKim Tae-Hee, Loe Adrian Kwan Ho, Zhu Lexinpp. 22-31TPX2 prompts mitotic survival via the induction of BCL2L1 through YAP1 protein stabilization in human embryonic stem cellsCha Hyuk-Jin, Kim Yun-Jeong, Go Young-Hyun, 정호창, Kwon Eun-Ji, Kim Seong-Min, Cheong Hyun Sub, Kim Wantae, Shin Hyoung Doo, Lee Haeseungpp. 32-42ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5Nam Hae Yun, 김성학, 김승후, 최경철, Park Seung-Ho, Song Ji-Hye, Jeong Ji-Hoon, Kim Hyunhee, Jeong Minseok, Kong Min-Jeong, Son Jihyun, Jeong Ji-Eunpp. 43-54
원문 보기