Nigericin-induced impairment of autophagic flux in neuronal cells is inhibited by overexpression of Bak

Junghyun Lim, Yunsu Lee, Hyun Wook Kim, Im Joo Rhyu, Myung Sook Oh, Moussa B H Youdim, Zhenyu Yue, Young J. Oh

Research output: Contribution to journalArticle

18 Citations (Scopus)


Bak is a prototypic pro-apoptotic Bcl-2 family protein expressed in a wide variety of tissues and cells. Recent studies have revealed that Bcl-2 family proteins regulate apoptosis as well as autophagy. To investigate whether and how Bak exerts a regulatory role on autophagy-related events, we treated independent cell lines, including MN9D neuronal cells, with nigericin, a K +/H+ ionophore. Treatment of MN9D cells with nigericin led to an increase of LC3-II and p62 levels with concomitant activation of caspase. Ultrastructural examination revealed accumulation of autophagic vacuoles and swollen vacuoles in nigericin-treated cells. We further found that the LC3-II accumulated as a consequence of impaired autophagic flux and the disrupted degradation of LC3-II in nigericin-treated cells. In this cell death paradigm, both transient and stable overexpression of various forms of Bak exerted a protective role, whereas it did not inhibit the extent of nigericin-mediated activation of caspase-3. Subsequent biochemical and electron microscopic studies revealed that overexpressed Bak maintained autophagic flux and reduced the area occupied by swollen vacuoles in nigericin- treated cells. Similar results were obtained in nigericin-treated non-neuronal cells and another proton ionophore-induced cell death paradigm. Taken together, our study indicates that a protective role for Bak during ionophore-induced cell death may be closely associated with its regulatory effect on maintenance of autophagic flux and vacuole homeostasis.

Original languageEnglish
Pages (from-to)23271-23282
Number of pages12
JournalJournal of Biological Chemistry
Issue number28
Publication statusPublished - 2012 Jul 6

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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