Ultrastructural evaluation of lithium-induced autophagic and mitochondrial stress in 3D endometrial and neuroblastoma spheroids

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Yıldırım B., Archibong-Omon A. A., Bilir A.

Scientific Reports, cilt.15, sa.1, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 1
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1038/s41598-025-21569-3
  • Dergi Adı: Scientific Reports
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Chemical Abstracts Core, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: 3D cancer spheroids, Endometrial cancer, Lithium chloride, Mitophagy, Transmission electron microscopy
  • İstanbul Üniversitesi Adresli: Evet

Özet

Lithium chloride (LiCl), a widely used mood stabilizer, has been reported to modulate selective autophagy pathways, including mitophagy. However, its ultrastructural effects in three-dimensional (3D) tumor models remain incompletely characterized. In this study, we examined the subcellular alterations induced by LiCl in 3D spheroid cultures derived from Ishikawa endometrial cancer and SH-SY5Y neuroblastoma cells. Spheroids were treated with 1, 10, or 50 mM LiCl and analyzed using transmission electron microscopy (TEM). The analysis revealed double-membrane-bound vesicles surrounding degenerating mitochondria, along with cytoplasmic vacuolization and membrane remodeling. These morphological features are suggestive of mitophagic activity, accompanied by stress-related ultrastructural remodeling. Although molecular validation (e.g., LC3B or PINK1/Parkin Western blotting) was not performed, the observed ultrastructural profiles are consistent with organelle-selective autophagy. These findings underscore the dose-dependent cellular responses to LiCl and support the value of 3D cancer spheroids as models to explore non-canonical autophagy-related stress pathways. Future studies incorporating molecular markers such as LC3B, PINK1, Parkin, and Lamin B1 will be essential to confirm these observations.