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Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells

Yıl 2026, Cilt: 53 Sayı: 1, 213 - 221, 10.03.2026
https://doi.org/10.5798/dicletip.1906491
https://izlik.org/JA56EE64SK

Öz

Background and Objective: Mitochondrial dynamics have a crucial role in the development of cancer and the plasticity of cancer cells. The role of mitochondria isolated from parental cells in regulating mitochondrial content and cancer stem cell (CSC) properties of MKN45 gastric cancer cells was examined.
Methods: Mitochondria were isolated from parental MKN45 cells and transferred into recipient cells using a co-incubation approach. Mitochondrial DNA (mtDNA) copy number was analyzed by quantitative real-time PCR (qPCR). Fluorescence microscopy was used to confirm the presence of mitochondria stained with Rhodamine 123 in the recipient cells following the transfer of mitochondria. Self-renewal capacity was evaluated using a sphere formation assay. The expression levels of stemness (OCT4, NANOG, BMI1), mesenchymal and epithelial (SNAIL, SLUG, VIMENTIN, E-CADHERIN) markers were determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR).
Results: The transfer of mitochondria caused a significant increase in the number of mtDNA copies and a higher mitochondrial membrane potential in the recipient cells. Furthermore, these mitochondrial alterations were functionally associated with an increase in the ability to form spheres and the expression of genes related to stemness, mesenchymal marker expression, and epithelial marker expression.
Conclusion: These results suggest that the augmented mitochondrial content enhances the CSC-like traits that could be a factor in tumor aggressiveness.

Kaynakça

  • 1.Lisowski P, Kannan P, Mlody B, et al. Mitochondriaand the dynamic control of stem cell homeostasis.EMBO Rep. 2018; 19(5):e45432.
  • 2.Vilà MR, Villarroya J, García-Arumí E, et al.Selective muscle fiber loss and molecularcompensation in mitochondrial myopathy due toTK2 deficiency. J Neurol Sci. 2008; 267(1–2): 137–41.
  • 3.Zhang X, Gao Y, Zhang S, et al. Mitochondrialdysfunction in the regulation of aging and aging-related diseases. Cell Commun Signal. 2025; 23(1):290.
  • 4.Xu X, Pang Y, Fan X. Mitochondria in oxidativestress, inflammation and aging: from mechanisms totherapeutic advances. Signal Transduct Target Ther.2025; 10(1): 190.
  • 5.Miyoshi N, Oubrahim H, Chock PB, et al. Age-dependent cell death and the role of ATP inhydrogen peroxide-induced apoptosis and necrosis.Proc Natl Acad Sci U S A. 2006; 103(6): 1727–31.
  • 6.Liberti MV, Locasale JW. The Warburg effect: howdoes it benefit cancer cells? Trends Biochem Sci.2016; 41(3): 211–18.
  • 7.Reznik E, Miller ML, Senbabaoğlu Y, et al.Mitochondrial DNA copy number variation acrosshuman cancers. eLife. 2016; 5: e10769.
  • 8.Zha J, Li J, Yin H, et al. TIMM23 overexpressiondrives NSCLC cell growth and survival by enhancingmitochondrial function. Cell Death Dis. 2025; 16(1):174.
  • 9.Agrawal A, Mabalirajan U. Rejuvenating cellularrespiration for optimizing respiratory function:targeting mitochondria. Am J Physiol Lung Cell MolPhysiol. 2016; 310(2): L103–13.
  • 10.Patananan AN, Wu T-H, Chiou P-Y, et al.Modifying the mitochondrial genome. Cell Metab.2016; 23(5): 785–96.
  • 11.Li X, Zhang Y, Yeung SC, et al. Mitochondrialtransfer of induced pluripotent stem cell–derivedmesenchymal stem cells to airway epithelial cellsattenuates cigarette smoke–induced damage. Am JRespir Cell Mol Biol. 2014; 51(3): 455–65.
  • 12.Zampieri LX, Silva-Almeida C, Rondeau JD, et al.Mitochondrial transfer in cancer: a comprehensivereview. Int J Mol Sci. 2021; 22(6).
  • 13.Chang J-C, Chang H-S, Wu Y-C, et al.Mitochondrial transplantation regulates antitumouractivity, chemoresistance and mitochondrialdynamics in breast cancer. J Exp Clin Cancer Res.2019; 38(1): 30.
  • 14.Liu X, Zhang Y, Yang X, et al. Mitochondrialtransplantation inhibits cholangiocarcinoma cellgrowth by balancing oxidative stress tolerancethrough PTEN/PI3K/AKT signaling pathway. TissueCell. 2023; 85: 102243.
  • 15.Rai NK, Mathur S, Singh SK, et al. Differentialregulation of mitochondrial complex I and oxidativestress based on metastatic potential of colorectalcancer cells. Oncol Lett. 2020; 20(6): 313.
  • 16.Livak KJ, Schmittgen TD. Analysis of relative geneexpression data using real-time quantitative PCRand the 2−ΔΔCT method. Methods. 2001; 25(4):402–08.
  • 17.Al Amir Dache Z, Thierry AR. Mitochondria-derived cell-to-cell communication. Cell Rep. 2023;42(7): 112728.
  • 18. Poulaki A, Giannouli S. Mitochondrial lipids: frommembrane organization to apoptotic facilitation. IntJ Mol Sci. 2022; 23(7).
  • 19.Franko A, Baris OR, Bergschneider E, et al.Efficient isolation of pure and functionalmitochondria from mouse tissues using automatedtissue disruption and enrichment with anti-TOM22magnetic beads. PLoS One. 2013; 8(12): e82392.
  • 20.Hornig-Do HT, Günther G, Bust M, et al. Isolationof functional pure mitochondria bysuperparamagnetic microbeads. Anal Biochem.2009; 389(1): 1–5.
  • 21.Liao PC, Bergamini C, Fato R, et al. Isolation ofmitochondria from cells and tissues. Methods CellBiol. 2020; 155: 3–31.
  • 22.Kim MJ, Hwang JW, Yun CK, et al. Delivery ofexogenous mitochondria via centrifugationenhances cellular metabolic function. Sci Rep. 2018;8(1): 3330.
  • 23.Headley CA, Gautam S. Extracellular delivery offunctional mitochondria rescues the dysfunction ofCD4(+) T cells in aging. Aging Cell. 2024; 11(5):e2303664.
  • 24.Li M, Wu L, Si H, et al. Engineered mitochondriain diseases: mechanisms, strategies, andapplications. Signal Transduct Target Ther. 2025;10(1): 71.
  • 25.Clemente-Suárez VJ, Martín-Rodríguez A.Mitochondrial transfer as a novel therapeuticapproach in disease diagnosis and treatment. Int JMol Sci. 2023; 24(10).
  • 26.Bocci F, Levine H, Onuchic JN, et al. Decipheringthe dynamics of epithelial-mesenchymal transitionand cancer stem cells in tumor progression. CurrStem Cell Rep. 2019; 5(1): 11–21.
  • 27.Yusri K, Jose S, Vermeulen KS, et al. The role ofNAD+ metabolism and its modulation ofmitochondria in aging and disease. NPJ MetabHealth Dis. 2025; 3(1): 26.
  • 28.Darvin PS, Sasidharan Nair V. Editorial:understanding mitochondrial dynamics andmetabolic plasticity in cancer stem cells. FrontOncol. 2023; 13.
  • 29.Guo X, Can C, Liu W, et al. Mitochondrial transferin hematological malignancies. Biomark Res. 2023;11(1): 89.
  • 30.Kubo Y, Tanaka K, Masuike Y, et al. Lowmitochondrial DNA copy number induceschemotherapy resistance via epithelial-mesenchymal transition by DNA methylation inesophageal squamous cancer cells. J Transl Med.2022; 20(1): 383.

Mitokondriyal Transferin Gastrik Kanser Hücrelerinde Kök Hücre Benzeri Özelliklerin Ortaya Çıkışındaki Rolü

Yıl 2026, Cilt: 53 Sayı: 1, 213 - 221, 10.03.2026
https://doi.org/10.5798/dicletip.1906491
https://izlik.org/JA56EE64SK

Öz

Amaç: Mitokondriyal dinamikler, kanserin gelişiminde ve kanser hücrelerinin plastisitesinde kritik bir rol oynamaktadır. Bu çalışmada, ebeveyn hücrelerden izole edilen mitokondrilerin MKN45 mide kanseri hücrelerinin mitokondriyal içeriği ve kanser kök hücresi (CSC) özellikleri üzerindeki rolü incelenmiştir.
Yöntemler: Mitokondriler, ebeveyn MKN45 hücrelerinden izole edilerek alıcı hücrelere birlikte inkübasyon yöntemiyle aktarıldı. Mitokondriyal DNA (mtDNA) kopya sayısı eş zamanlı qPCR ile analiz edildi. Mitokondri transferinden sonra alıcı hücrelerde Rhodamine 123 ile boyanmış mitokondri varlığını doğrulamak için floresan mikroskopi kullanıldı. Öz yenilenme kapasitesini değerlendirmek için küre (sphere) oluşum analizi yapıldı ve kök hücre belirteçleri (OCT4, NANOG, BMI1) ile mezenkimal ve epitelyal belirteçlerin (SNAIL, SLUG, VIMENTIN, E-KADERİN) gen ekspresyon düzeyleri RT-qPCR ile belirlendi.
Bulgular: Mitokondrilerin aktarımı, alıcı hücrelerde mtDNA kopya sayısında dikkat çekici bir artışa ve daha yüksek bir mitokondriyal membran potansiyeline neden olmuştur. Ayrıca, bu mitokondriyal değişikliklerin, küre (sphere) oluşturma yeteneğinde ve kök hücreliliğe (stemness) ilişkin genlerin (OCT4, NANOG, BMI1) yanı sıra mezenkimal ve epitelyal belirteçlerin (SNAIL, SLUG, VIMENTIN, E-KADERİN) ekspresyonunda artışla işlevsel olarak bağlantılı olduğu görülmüştür.
Sonuç: Bu sonuçlar, artan mitokondriyal içeriğin CSC özelliklerini güçlendirdiğini ve bunun tümör agresifliğinde etkili bir faktör olabileceğini düşündürmektedir.

Kaynakça

  • 1.Lisowski P, Kannan P, Mlody B, et al. Mitochondriaand the dynamic control of stem cell homeostasis.EMBO Rep. 2018; 19(5):e45432.
  • 2.Vilà MR, Villarroya J, García-Arumí E, et al.Selective muscle fiber loss and molecularcompensation in mitochondrial myopathy due toTK2 deficiency. J Neurol Sci. 2008; 267(1–2): 137–41.
  • 3.Zhang X, Gao Y, Zhang S, et al. Mitochondrialdysfunction in the regulation of aging and aging-related diseases. Cell Commun Signal. 2025; 23(1):290.
  • 4.Xu X, Pang Y, Fan X. Mitochondria in oxidativestress, inflammation and aging: from mechanisms totherapeutic advances. Signal Transduct Target Ther.2025; 10(1): 190.
  • 5.Miyoshi N, Oubrahim H, Chock PB, et al. Age-dependent cell death and the role of ATP inhydrogen peroxide-induced apoptosis and necrosis.Proc Natl Acad Sci U S A. 2006; 103(6): 1727–31.
  • 6.Liberti MV, Locasale JW. The Warburg effect: howdoes it benefit cancer cells? Trends Biochem Sci.2016; 41(3): 211–18.
  • 7.Reznik E, Miller ML, Senbabaoğlu Y, et al.Mitochondrial DNA copy number variation acrosshuman cancers. eLife. 2016; 5: e10769.
  • 8.Zha J, Li J, Yin H, et al. TIMM23 overexpressiondrives NSCLC cell growth and survival by enhancingmitochondrial function. Cell Death Dis. 2025; 16(1):174.
  • 9.Agrawal A, Mabalirajan U. Rejuvenating cellularrespiration for optimizing respiratory function:targeting mitochondria. Am J Physiol Lung Cell MolPhysiol. 2016; 310(2): L103–13.
  • 10.Patananan AN, Wu T-H, Chiou P-Y, et al.Modifying the mitochondrial genome. Cell Metab.2016; 23(5): 785–96.
  • 11.Li X, Zhang Y, Yeung SC, et al. Mitochondrialtransfer of induced pluripotent stem cell–derivedmesenchymal stem cells to airway epithelial cellsattenuates cigarette smoke–induced damage. Am JRespir Cell Mol Biol. 2014; 51(3): 455–65.
  • 12.Zampieri LX, Silva-Almeida C, Rondeau JD, et al.Mitochondrial transfer in cancer: a comprehensivereview. Int J Mol Sci. 2021; 22(6).
  • 13.Chang J-C, Chang H-S, Wu Y-C, et al.Mitochondrial transplantation regulates antitumouractivity, chemoresistance and mitochondrialdynamics in breast cancer. J Exp Clin Cancer Res.2019; 38(1): 30.
  • 14.Liu X, Zhang Y, Yang X, et al. Mitochondrialtransplantation inhibits cholangiocarcinoma cellgrowth by balancing oxidative stress tolerancethrough PTEN/PI3K/AKT signaling pathway. TissueCell. 2023; 85: 102243.
  • 15.Rai NK, Mathur S, Singh SK, et al. Differentialregulation of mitochondrial complex I and oxidativestress based on metastatic potential of colorectalcancer cells. Oncol Lett. 2020; 20(6): 313.
  • 16.Livak KJ, Schmittgen TD. Analysis of relative geneexpression data using real-time quantitative PCRand the 2−ΔΔCT method. Methods. 2001; 25(4):402–08.
  • 17.Al Amir Dache Z, Thierry AR. Mitochondria-derived cell-to-cell communication. Cell Rep. 2023;42(7): 112728.
  • 18. Poulaki A, Giannouli S. Mitochondrial lipids: frommembrane organization to apoptotic facilitation. IntJ Mol Sci. 2022; 23(7).
  • 19.Franko A, Baris OR, Bergschneider E, et al.Efficient isolation of pure and functionalmitochondria from mouse tissues using automatedtissue disruption and enrichment with anti-TOM22magnetic beads. PLoS One. 2013; 8(12): e82392.
  • 20.Hornig-Do HT, Günther G, Bust M, et al. Isolationof functional pure mitochondria bysuperparamagnetic microbeads. Anal Biochem.2009; 389(1): 1–5.
  • 21.Liao PC, Bergamini C, Fato R, et al. Isolation ofmitochondria from cells and tissues. Methods CellBiol. 2020; 155: 3–31.
  • 22.Kim MJ, Hwang JW, Yun CK, et al. Delivery ofexogenous mitochondria via centrifugationenhances cellular metabolic function. Sci Rep. 2018;8(1): 3330.
  • 23.Headley CA, Gautam S. Extracellular delivery offunctional mitochondria rescues the dysfunction ofCD4(+) T cells in aging. Aging Cell. 2024; 11(5):e2303664.
  • 24.Li M, Wu L, Si H, et al. Engineered mitochondriain diseases: mechanisms, strategies, andapplications. Signal Transduct Target Ther. 2025;10(1): 71.
  • 25.Clemente-Suárez VJ, Martín-Rodríguez A.Mitochondrial transfer as a novel therapeuticapproach in disease diagnosis and treatment. Int JMol Sci. 2023; 24(10).
  • 26.Bocci F, Levine H, Onuchic JN, et al. Decipheringthe dynamics of epithelial-mesenchymal transitionand cancer stem cells in tumor progression. CurrStem Cell Rep. 2019; 5(1): 11–21.
  • 27.Yusri K, Jose S, Vermeulen KS, et al. The role ofNAD+ metabolism and its modulation ofmitochondria in aging and disease. NPJ MetabHealth Dis. 2025; 3(1): 26.
  • 28.Darvin PS, Sasidharan Nair V. Editorial:understanding mitochondrial dynamics andmetabolic plasticity in cancer stem cells. FrontOncol. 2023; 13.
  • 29.Guo X, Can C, Liu W, et al. Mitochondrial transferin hematological malignancies. Biomark Res. 2023;11(1): 89.
  • 30.Kubo Y, Tanaka K, Masuike Y, et al. Lowmitochondrial DNA copy number induceschemotherapy resistance via epithelial-mesenchymal transition by DNA methylation inesophageal squamous cancer cells. J Transl Med.2022; 20(1): 383.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi, Tıp Eğitimi, Sağlık Hizmetleri ve Sistemleri (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Özlem Türksoy Terzioğlu

Gokhan Terzioglu

Gönderilme Tarihi 28 Ekim 2025
Kabul Tarihi 6 Mart 2026
Yayımlanma Tarihi 10 Mart 2026
DOI https://doi.org/10.5798/dicletip.1906491
IZ https://izlik.org/JA56EE64SK
Yayımlandığı Sayı Yıl 2026 Cilt: 53 Sayı: 1

Kaynak Göster

APA Türksoy Terzioğlu, Ö., & Terzioglu, G. (2026). Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells. Dicle Medical Journal, 53(1), 213-221. https://doi.org/10.5798/dicletip.1906491
AMA 1.Türksoy Terzioğlu Ö, Terzioglu G. Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells. diclemedj. 2026;53(1):213-221. doi:10.5798/dicletip.1906491
Chicago Türksoy Terzioğlu, Özlem, ve Gokhan Terzioglu. 2026. “Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells”. Dicle Medical Journal 53 (1): 213-21. https://doi.org/10.5798/dicletip.1906491.
EndNote Türksoy Terzioğlu Ö, Terzioglu G (01 Mart 2026) Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells. Dicle Medical Journal 53 1 213–221.
IEEE [1]Ö. Türksoy Terzioğlu ve G. Terzioglu, “Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells”, diclemedj, c. 53, sy 1, ss. 213–221, Mar. 2026, doi: 10.5798/dicletip.1906491.
ISNAD Türksoy Terzioğlu, Özlem - Terzioglu, Gokhan. “Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells”. Dicle Medical Journal 53/1 (01 Mart 2026): 213-221. https://doi.org/10.5798/dicletip.1906491.
JAMA 1.Türksoy Terzioğlu Ö, Terzioglu G. Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells. diclemedj. 2026;53:213–221.
MLA Türksoy Terzioğlu, Özlem, ve Gokhan Terzioglu. “Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells”. Dicle Medical Journal, c. 53, sy 1, Mart 2026, ss. 213-21, doi:10.5798/dicletip.1906491.
Vancouver 1.Özlem Türksoy Terzioğlu, Gokhan Terzioglu. Mitochondrial Transfer Drives Stem Cell–Like Phenotypes in Gastric Cancer Cells. diclemedj. 01 Mart 2026;53(1):213-21. doi:10.5798/dicletip.1906491