Mitochondrial autophagy as a compensatory response to PINK1 deficiency

Salvatore J. Cherra, Ruben K. Dagda, Anurag Tandon, Charleen T. Chu

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Macroautophagy (hereafter, autophagy) plays a critical role in maintaining cellular homeostasis by degrading protein aggregates and dysfunctional/ damaged organelles. We recently reported that silencing the recessive familial Parkinson disease gene encoding PTEN-induced kinase 1 (PINK1) leads to neuronal cell death accompanied by mitochondrial dysfunction and Drp1-dependent fragmentation. In this model, mitochondrial fission and Beclin 1-dependent autophagy play protective roles, cooperating to sequester and eliminate damaged mitochondria. We discuss the role of superoxide and other reactive oxygen species upstream of mitochondrial depolarization, fission and autophagy in PINK1 knockdown lines. PINK1 deficiency appears to trigger several compensatory responses that together facilitate clearance of depolarized mitochondria, through a mechanism that is further enhanced by increased expression of parkin. These data offer additional insights that broaden the spectrum of potential interactions between PINK1 and parkin with respect to the regulation of mitochondrial homeostasis and mitophagy.

Original languageEnglish
Pages (from-to)1213-1214
Number of pages2
JournalAutophagy
Volume5
Issue number8
DOIs
StatePublished - Nov 16 2009

Bibliographical note

Funding Information:
Supported by funding from the National Institutes of Health (AG026389, R01 supplement AG026389-03W1 and NS053777). S.J.C. was supported in part by F31 NS064728 and R.K.D. by F32 AG030821.

Keywords

  • Autophagy
  • Beclin 1
  • Cell death
  • Mitochondria
  • PINK1
  • Parkin
  • Parkinson disease

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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