Tauroursodeoxycholic Acid Protects Against Mitochondrial Dysfunction and Cell Death via Mitophagy in Human Neuroblastoma Cells

Inês Fonseca, Gisela Gordino, Sara Moreira, Maria João Nunes, Carla Azevedo, Maria João Gama, Elsa Rodrigues, Cecília Maria Pereira Rodrigues, Margarida Castro-Caldas

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Mitochondrial dysfunction has been deeply implicated in the pathogenesis of several neurodegenerative diseases. Thus, to keep a healthy mitochondrial population, a balanced mitochondrial turnover must be achieved. Tauroursodeoxycholic acid (TUDCA) is neuroprotective in various neurodegenerative disease models; however, the mechanisms involved are still incompletely characterized. In this study, we investigated the neuroprotective role of TUDCA against mitochondrial damage triggered by the mitochondrial uncoupler carbonyl cyanide m-chlorophelyhydrazone (CCCP). Herein, we show that TUDCA significantly prevents CCCP-induced cell death, ROS generation, and mitochondrial damage. Our results indicate that the neuroprotective role of TUDCA in this cell model is mediated by parkin and depends on mitophagy. The demonstration that pharmacological up-regulation of mitophagy by TUDCA prevents neurodegeneration provides new insights for the use of TUDCA as a modulator of mitochondrial activity and turnover, with implications in neurodegenerative diseases.

Original languageEnglish
Pages (from-to)6107-6119
JournalMolecular Neurobiology
Volume54
Issue number8
DOIs
Publication statusE-pub ahead of print - 3 Oct 2016

Keywords

  • Autophagy
  • Mitochondria
  • Mitophagy
  • Parkin
  • SH-SY5Y cells
  • TUDCA

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