Targeting enhanced mitochondrial respiration chain activity as a potential therapeutic approach for endometriosis

Katarína Kalinová, Benjamin Gottschalk, Martin Hirtl, Julian Ostaku, Ostaku J, Sonja Gabrijelčič, Alwin Sokolowski, Sokolowski A, Ernst Malle, Malle E, Wolfgang F. Graier, Graier WF, Corina T. Madreiter‐Sokolowski, Madreiter-Sokolowski CT, Corina T Madreiter-Sokolowski
Biochimica et biophysica acta. Molecular basis of disease · 2025 · vol. 1871(6) , pp. 167885 · doi:10.1016/j.bbadis.2025.167885 · PMID:40320187 · W4410023162
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Endometriotic cells exhibit enhanced mitochondrial respiration and Ca2+ uptake, similar to cancer cells, making them susceptible to treatments targeting the electron transport chain or ATP synthase.

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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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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