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

Katarína Kalinová, Benjamin Gottschalk, Martin Hirtl, Julian Ostaku, Sonja Gabrijelčič, Alwin Sokolowski, Ernst Malle, Wolfgang F Graier, Corina T. Madreiter‐Sokolowski, 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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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

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 Ca 2+ uptake. However, an increase in the reduction equivalent yield and oxygen consumption rate was exclusively found in 12Z cells, whereas the reduced ΔΨ m and the reverse mode of F O F 1 -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 F O F 1 -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 F O F 1 -ATP synthase may represent a promising new treatment strategy for endometriosis. • Endometriotic cells share features with cancer cells in mitochondrial and cristae morphology. • Endometriotic cells show increased mitochondrial calcium uptake, reduction equivalent yield, oxygen consumption rate, and mitochondrial ATP production. • Endometriotic cells exhibit an increased reverse activity of F O F 1 -ATP synthase, potentially counteracting mitochondrial membrane potential loss. • Quercetin effectively kills endometriotic and cancer cells while sparing non-cancerous cells. • Targeting the reverse activity of F O F 1 -ATP synthase might offer a new treatment strategy for endometriosis.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

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

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