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Parsiyal Hepatektomi ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması

Year 2025, Volume: 29 Issue: 2, 360 - 365, 25.08.2025
https://doi.org/10.19113/sdufenbed.1526397

Abstract

Karaciğer rejenerasyonu çok sayıda kompleksin görev aldığı karmaşık bir mekanizmadır. Rejenerasyon, karaciğerin %70’nin çıkarılmasıyla tetiklenir ve hücreler, 1-2 bölünmeden sonra tekrar G0 fazına geçer. Karaciğer rejenerasyonu sırasında mitokondrilerin şekilsel olarak bozulduğu, krista sayının arttığı, şiştiği ancak; ilerleyen saatlerde normale döndüğü bilinmektedir. Karaciğer rejenerasyonu sırasında mitokondrilerin nasıl normale döndüğü ile ilgili moleküler mekanizmalar açık değildir. Mitokondrilerin, günümüzde, enerji üretimi dışında farklı mekanizmalarla (mitofaji, mitokondriyal fizyon, kalsiyum homeostazisi Fe-S protein sentezi gibi) ilişkisi açıktır. Bu nedenle çalışmamızda parsiyal hepatektomi ile tetiklenen karaciğer rejenerasyonunda Drp1 gen ekspresyonu ve DRP1, MUL1 protein miktarları belirlenerek MUL1 aracılı mitofaji/mitokondriyal fizyon mekanizmasının olası aktivasyonu rejenerasyonun 6, 12, 24 saatlerine göre değerlendirilmiştir. Elde edilen veriler sonucunda; MUL1 protein miktarlarında; PH rejenerasyon gruplarında, Sham gruplarına göre düşüş olduğu belirlenmiştir. Drp1 değerlendirildiğinde genel olarak PH gruplarında düşmesine rağmen PH12. saatte meydana gelen hafif artış ilginçtir. Drp1 ekspresyonu ve protein miktarındaki bu artışın mitofajiden ziyade farklı mekanizmalarla (Kalsiyum homeostazı, ERAD) ilişkili olabileceğini düşündürüyor. Bunun için daha fazla araştırmaya ihtiyaç vardır.

Project Number

FEF19001.22.005

References

  • [1] Chen, S., Zheng, J., Hao, Q., Yang, S., Wang, J., Chen, H., Chen, L., Zhou, Y., Yu, C., Jiao, B., Cai, Z., 2010. p53-insensitive PUMA down-regulation is essential in the early phase of liver regeneration after partial hepatectomy in mice. Journal of Hepatology, 52, 864–71.
  • [2] Fausto, N. 2000. Liver regeneration. Journal of Hepatology, 32, 19–31.
  • [3] Starkel, P., De Saeger, C., Sempoux, C., Legrand, E., Leclercq, I., Horsmans, Y., 2005. Blunted DNA synthesis and delayed S-phase entry following inhibition of Cdk2 activity in the regenerating rat liver. Laboratory Investigation, 85(4), 562–571.
  • [4] Viragh, S., Bartok, I., 1966, An electron microscopic study of the regeneration of the liver following partial hepatectomy. The Journal of Laryngology & Otology, 549(5), 825-839.
  • [5] Ferri, D., Moro, L., Mastrodonato, M., Capuano, F., Marra, E., Liquori, GE., Greco, M., 2005. Ultrastructural zonal heterogeneity of hepatocytes and mitochondria within the hepatic acinus during liver regeneration after partial hepatectomy. Biology of the Cell, 97(4), 277–288 .
  • [6] Guerrıerı, F., Vendemıale, G., Grattaglıano, I., Cocco, T., Pellecchıa, G vd., 1999, Mıtochondrıal Oxıdatıve Alteratıons Followıng Partıal Hepatectomy, Free Radical Biology and Medicine, 26(1-2), 34–41.
  • [7] Choubey V., Zeb A, Kaasik A., 2022. Molecular mechanisms and regulation of mammalian mitophagy. Cells 11(1):1-38.
  • [8] Peng, J., Ren, K. Di., Yang, J., Luo, XJ., 2016. Mitochondrial E3 ubiquitin ligase 1: A key enzyme in regulation of mitochondrial dynamics and functions, Mitochondrion, 28, 49–53.
  • [9] Youle, R. J., Van Der Bliek, A. M., 2012. Mitochondrial fission, fusion and stress. Science, 337(6098):1062–1065.
  • [10] Villa, E., Marchetti, S., Ricci, J. E., 2018. No Parkin zone: Mitophagy without Parkin. Trends in Cell Biology, 28(11), 882–895.
  • [11] Ozmen Yaylaci A, Canbek M., 2023. The role of ubiquitin signaling pathway on liver regeneration in rats. Molecular and Cellular Biochemistry, 478, 131e47.
  • [12] Higgins, GM, Anderson, RM, 1931. Experimental pathology of liver. I. Restroration of liver white rat following partial surgical removal. Arch. Pathol., 12, 186–202.
  • [13] Livak, K. J., Schmittgen, T. D., 2001. Analysis of relative gene expression data using Real-Time Quantitative PCR and the 2-∆∆Ct Method. Methods, 25, 402–408.
  • [14] Fernandes, K. A., Harder, J. M., Kim, J., Libby, R. T., 2013. JUN regulates early transcriptional responses to axonal injury in retinal ganglion cells. Experimental Eye Research, 112, 106–117.
  • [15] Yang D., Ying J., Wang X., Zhao T., Yoon, S., Fang, Y., Zheng, Q., Liu, X., Yu, W., Hua, F., 2021. Mitochondrial Dynamics: A Key role in neurodegeneration and a potential target for neurodegenerative disease. Frontiers in Neuroscience, 15 (654785), 1-13.
  • [16] Zhong Z., Rehman H., Krishnasamy Y., Liu, Q., Shi, Y., Schnellmann, RG., 2011. Alterations of mitochondrial homeostasis after ischemia/reperfusion (IR) and partial hepatectomy (PHX) in mice. Experimental Biology 2011 Meeting Abstracts, 25(S1).
  • [17] Chen CW, Su C, Huang CY, Huang XY, Cuili X, Chao T, Fan CH, Ting CW, Tsai YW, Yang KC, Yeh TY, Hsieh ST, Chen YJ, Feng Y, Hunter T, Chang ZF., 2024. NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia, Nature Communications,
  • [18] Liu Q, Dong Q 2020. NR4A2 Exacerbates cerebral ischemic brain injury via modulating microRNA 652/Mul1pathway, Neuropsychiatric Disease and Treatment, 16:2285-2296.
  • [19] Michalopoulos GK, 2007. Liver regeneration, Journal of Cellular Physiology, Mini Review.
  • [20] He S, Atkinson C, Qiao F, Cianflone K, Chen X, Tomlinson S, 2009. A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice, The Journal of Clinical Investigation, The Journal of Clinical Investigation, 19(8):2304-2316.
  • [21]Schadde E, Tsatsaris C, Swiderska-Syn M, Breitenstein Urner M,Schimmer R, Booya C, Z’graggen BR, Wenger RH, Spahn DR, Hertl M, Knechtle S, Diehl AM, Schl€apfer M, Beck Schimmer B, 2016. Hypoxia of the growing liver accelerates regeneration, sURGERY, 161(3):671 678.
  • [22] Maeno H, Ono T, Dhar DK, Sato T, Yamanoi A, Nagasue N. 2005. Expression of hypoxia inducible factor-1a during liver regeneration induced by partial hepatectomy in rats, Liver International, 25:1002-1009.

Investigation of Possible Mitochondrial Fission Mechanism in Liver Regeneration Triggered by Partial Hepatectomy

Year 2025, Volume: 29 Issue: 2, 360 - 365, 25.08.2025
https://doi.org/10.19113/sdufenbed.1526397

Abstract

Liver regeneration is a complex mechanism in which a large number of complexes are involved. Regeneration is triggered by the removal of 70% of the liver, and the cells go back into the G0 phase after 1-2 divisions. It is known that during liver regeneration, mitochondria are deformed, swollen, increased crista. In the later hours of regeneration, it is observed that mitochondria return to normal. The molecular mechanisms involved in how mitochondria return to normal during liver regeneration are not clear. Mitochondria do not only produce energy; It is also associated with the mechanisms of mitophagy, mitochondrial fission, calcium homeostasis, Fe-S protein synthesis. In our study, Drp1 gene expression and DRP1, MUL1 protein amounts were determined according to 6, 12, 24 hours of regeneration As a result of the data obtained; MUL1 protein amounts were decreased in the PH groups compared to the sham groups. Although Drp1 expression and DRP1 protein quantities generally fall in PH groups, the slight increase in PH12 is interesting. We think that Drp1 expression and an increase in protein amount may be related to different mechanisms from mitophagy (Calcium homeostasis, ERAD). We think that Drp1 expression and protein quantity increases may be related to different mechanisms (Calcium homeostasis, ERAD) than mitophagy. More researches are needed.

Project Number

FEF19001.22.005

References

  • [1] Chen, S., Zheng, J., Hao, Q., Yang, S., Wang, J., Chen, H., Chen, L., Zhou, Y., Yu, C., Jiao, B., Cai, Z., 2010. p53-insensitive PUMA down-regulation is essential in the early phase of liver regeneration after partial hepatectomy in mice. Journal of Hepatology, 52, 864–71.
  • [2] Fausto, N. 2000. Liver regeneration. Journal of Hepatology, 32, 19–31.
  • [3] Starkel, P., De Saeger, C., Sempoux, C., Legrand, E., Leclercq, I., Horsmans, Y., 2005. Blunted DNA synthesis and delayed S-phase entry following inhibition of Cdk2 activity in the regenerating rat liver. Laboratory Investigation, 85(4), 562–571.
  • [4] Viragh, S., Bartok, I., 1966, An electron microscopic study of the regeneration of the liver following partial hepatectomy. The Journal of Laryngology & Otology, 549(5), 825-839.
  • [5] Ferri, D., Moro, L., Mastrodonato, M., Capuano, F., Marra, E., Liquori, GE., Greco, M., 2005. Ultrastructural zonal heterogeneity of hepatocytes and mitochondria within the hepatic acinus during liver regeneration after partial hepatectomy. Biology of the Cell, 97(4), 277–288 .
  • [6] Guerrıerı, F., Vendemıale, G., Grattaglıano, I., Cocco, T., Pellecchıa, G vd., 1999, Mıtochondrıal Oxıdatıve Alteratıons Followıng Partıal Hepatectomy, Free Radical Biology and Medicine, 26(1-2), 34–41.
  • [7] Choubey V., Zeb A, Kaasik A., 2022. Molecular mechanisms and regulation of mammalian mitophagy. Cells 11(1):1-38.
  • [8] Peng, J., Ren, K. Di., Yang, J., Luo, XJ., 2016. Mitochondrial E3 ubiquitin ligase 1: A key enzyme in regulation of mitochondrial dynamics and functions, Mitochondrion, 28, 49–53.
  • [9] Youle, R. J., Van Der Bliek, A. M., 2012. Mitochondrial fission, fusion and stress. Science, 337(6098):1062–1065.
  • [10] Villa, E., Marchetti, S., Ricci, J. E., 2018. No Parkin zone: Mitophagy without Parkin. Trends in Cell Biology, 28(11), 882–895.
  • [11] Ozmen Yaylaci A, Canbek M., 2023. The role of ubiquitin signaling pathway on liver regeneration in rats. Molecular and Cellular Biochemistry, 478, 131e47.
  • [12] Higgins, GM, Anderson, RM, 1931. Experimental pathology of liver. I. Restroration of liver white rat following partial surgical removal. Arch. Pathol., 12, 186–202.
  • [13] Livak, K. J., Schmittgen, T. D., 2001. Analysis of relative gene expression data using Real-Time Quantitative PCR and the 2-∆∆Ct Method. Methods, 25, 402–408.
  • [14] Fernandes, K. A., Harder, J. M., Kim, J., Libby, R. T., 2013. JUN regulates early transcriptional responses to axonal injury in retinal ganglion cells. Experimental Eye Research, 112, 106–117.
  • [15] Yang D., Ying J., Wang X., Zhao T., Yoon, S., Fang, Y., Zheng, Q., Liu, X., Yu, W., Hua, F., 2021. Mitochondrial Dynamics: A Key role in neurodegeneration and a potential target for neurodegenerative disease. Frontiers in Neuroscience, 15 (654785), 1-13.
  • [16] Zhong Z., Rehman H., Krishnasamy Y., Liu, Q., Shi, Y., Schnellmann, RG., 2011. Alterations of mitochondrial homeostasis after ischemia/reperfusion (IR) and partial hepatectomy (PHX) in mice. Experimental Biology 2011 Meeting Abstracts, 25(S1).
  • [17] Chen CW, Su C, Huang CY, Huang XY, Cuili X, Chao T, Fan CH, Ting CW, Tsai YW, Yang KC, Yeh TY, Hsieh ST, Chen YJ, Feng Y, Hunter T, Chang ZF., 2024. NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia, Nature Communications,
  • [18] Liu Q, Dong Q 2020. NR4A2 Exacerbates cerebral ischemic brain injury via modulating microRNA 652/Mul1pathway, Neuropsychiatric Disease and Treatment, 16:2285-2296.
  • [19] Michalopoulos GK, 2007. Liver regeneration, Journal of Cellular Physiology, Mini Review.
  • [20] He S, Atkinson C, Qiao F, Cianflone K, Chen X, Tomlinson S, 2009. A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice, The Journal of Clinical Investigation, The Journal of Clinical Investigation, 19(8):2304-2316.
  • [21]Schadde E, Tsatsaris C, Swiderska-Syn M, Breitenstein Urner M,Schimmer R, Booya C, Z’graggen BR, Wenger RH, Spahn DR, Hertl M, Knechtle S, Diehl AM, Schl€apfer M, Beck Schimmer B, 2016. Hypoxia of the growing liver accelerates regeneration, sURGERY, 161(3):671 678.
  • [22] Maeno H, Ono T, Dhar DK, Sato T, Yamanoi A, Nagasue N. 2005. Expression of hypoxia inducible factor-1a during liver regeneration induced by partial hepatectomy in rats, Liver International, 25:1002-1009.
There are 22 citations in total.

Details

Primary Language Turkish
Subjects Cell Development, Proliferation and Death
Journal Section Articles
Authors

Ayşe Özmen Yaylacı 0000-0001-9658-3316

Mediha Canbek 0000-0003-1095-2382

Project Number FEF19001.22.005
Publication Date August 25, 2025
Submission Date August 1, 2024
Acceptance Date June 26, 2025
Published in Issue Year 2025 Volume: 29 Issue: 2

Cite

APA Özmen Yaylacı, A., & Canbek, M. (2025). Parsiyal Hepatektomi ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 29(2), 360-365. https://doi.org/10.19113/sdufenbed.1526397
AMA Özmen Yaylacı A, Canbek M. Parsiyal Hepatektomi ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması. J. Nat. Appl. Sci. August 2025;29(2):360-365. doi:10.19113/sdufenbed.1526397
Chicago Özmen Yaylacı, Ayşe, and Mediha Canbek. “Parsiyal Hepatektomi Ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması”. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi 29, no. 2 (August 2025): 360-65. https://doi.org/10.19113/sdufenbed.1526397.
EndNote Özmen Yaylacı A, Canbek M (August 1, 2025) Parsiyal Hepatektomi ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi 29 2 360–365.
IEEE A. Özmen Yaylacı and M. Canbek, “Parsiyal Hepatektomi ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması”, J. Nat. Appl. Sci., vol. 29, no. 2, pp. 360–365, 2025, doi: 10.19113/sdufenbed.1526397.
ISNAD Özmen Yaylacı, Ayşe - Canbek, Mediha. “Parsiyal Hepatektomi Ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması”. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi 29/2 (August2025), 360-365. https://doi.org/10.19113/sdufenbed.1526397.
JAMA Özmen Yaylacı A, Canbek M. Parsiyal Hepatektomi ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması. J. Nat. Appl. Sci. 2025;29:360–365.
MLA Özmen Yaylacı, Ayşe and Mediha Canbek. “Parsiyal Hepatektomi Ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması”. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, vol. 29, no. 2, 2025, pp. 360-5, doi:10.19113/sdufenbed.1526397.
Vancouver Özmen Yaylacı A, Canbek M. Parsiyal Hepatektomi ile Tetiklenen Karaciğer Rejenerasyonunda Olası Mitokondriyal Fizyon Mekanizmasının Araştırılması. J. Nat. Appl. Sci. 2025;29(2):360-5.

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