Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kalinová, K; Gottschalk, B; Hirtl, M; Ostaku, J; Gabrijelčič, S; Sokolowski, A; Malle, E; Graier, WF; Madreiter-Sokolowski, CT.
Targeting enhanced mitochondrial respiration chain activity as a potential therapeutic approach for endometriosis.
Biochim Biophys Acta Mol Basis Dis. 2025; 167885
Doi: 10.1016/j.bbadis.2025.167885
PubMed
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- Führende Autor*innen der Med Uni Graz
- Kalinova Katarina
- Madreiter-Sokolowski Corina
- Co-Autor*innen der Med Uni Graz
- Gabrijelcic Sonja
- Gottschalk Benjamin
- Graier Wolfgang
- Hirtl Martin
- Malle Ernst
- Ostaku Julian
- Sokolowski Alwin
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- Abstract:
- Endometriosis is a chronic condition defined by the presence of endometrial-like tissue outside the uterus. Since endometriotic cells share similarities with cancer cells, including uncontrolled cell growth and invasion, we investigated whether cancer cell-specific rewiring of mitochondrial signaling is also present in endometriotic cells. We utilized the endometriotic cell line 12Z and investigated its mitochondrial function in comparison with the uterine cancer cell line SK-UT-1 and the mammary epithelial cell line hTERT-HME1. We could show that the endometriotic 12Z cells share structural similarities with cancerous SK-UT-1 cells with enhanced colocalization between the endoplasmic reticulum and mitochondria and increased cristae width and density associated with facilitated mitochondrial Ca2+ uptake. However, an increase in the reduction equivalent yield and oxygen consumption rate was exclusively found in 12Z cells, whereas the reduced ΔΨm and the reverse mode of FOF1-ATP synthase were also detected in SK-UT-1 cells. These features rendered both cell types susceptible to quercetin and oligomycin A treatment. We assume that the complexes of the electron transport chain and the FOF1-ATP synthase in reverse mode have a crucial role in maintaining mitochondrial membrane potential and, thereby, mitochondrial integrity of endometriotic 12Z cells. Therefore, targeting the electron transport chain or the reverse mode of FOF1-ATP synthase may represent a promising new treatment strategy for endometriosis.