Dysregulated autophagy is linked to BAX oligomerization and subsequent cytochrome c release in 6-hydroxydopmaine-treated neuronal cells

Yuhyun Chung, Yoonkyung Kim, Nuri Yun, Young J. Oh

Research output: Contribution to journalArticlepeer-review

Abstract

Autophagy and apoptosis are essential physiological pathways that are required to maintain cellular homeostasis. Therefore, it is suggested that dysregulation in both pathways is linked to several disease states. Moreover, the crosstalk between autophagy and apoptosis plays an important role in pathophysiological processes associated with several neurodegenerative disorders. We have previously reported that 6-hydroxydopamine (6-OHDA)-triggered reactive oxygen species (ROS) induces dysregulated autophagy, and that a dysregulated autophagic flux contributes to caspase-dependent neuronal apoptosis. Based on our previous findings, we specifically aimed to elucidate the molecular mechanisms underlying the potential role of dysregulated autophagy in apoptotic neurodegeneration. The disuccinimidyl suberate (DSS) cross-linking assay and immunological analyses indicated that exposure of several types of cells to 6-OHDA resulted in BAX activation and subsequent oligomerization. Pharmacological inhibition and genetic perturbation of autophagy prevented 6-OHDA-induced BAX oligomerization and subsequent release of mitochondrial cytochrome c into the cytosol and caspase activation. These events were independent of expression levels of XIAP. Taken together, our results suggest that BAX oligomerization comprises a critical step by which 6-OHDA-induced dysregulated autophagy mediates neuronal apoptosis.

Original languageEnglish
Pages (from-to)20-26
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume548
DOIs
Publication statusPublished - 2021 Apr 9

Bibliographical note

Funding Information:
This work was supported by the Small Grant for Exploratory Research program ( 2018R1D1A1A02085731 to NY) through the National Research Foundation of Korea (NRF) grant funded by Ministry of Education and by the Brain Research Program ( 2017M37A1025369 to YJO) and by the Mid-Career Research Program ( 2019R1A2C1088793 to YJO) through the NRF grant funded by Ministry of Science and ICT.

Publisher Copyright:
© 2021 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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