Parkin and mitofusins reciprocally regulate mitophagy and mitochondrial spheroid formation

Wen Xing Ding, Fengli Guo, Hong Min Ni, Abigail Bockus, Sharon Manley, Donna B. Stolz, Eeva Liisa Eskelinen, Hartmut Jaeschke, Xiao Ming Yin

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Mitochondrial homeostasis via mitochondrial dynamics and quality control is crucial to normal cellular functions. Mitophagy (mitochondria removed by autophagy) stimulated by a mitochondrial uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP), requires Parkin, but it is not clear why Parkin is crucial to this process. We found that in the absence of Parkin, carbonyl cyanide m-chlorophenylhydrazone induced the formation of mitochondrial spheroids. Mitochondrial spheroid formation is also induced in vivo in the liver by acetaminophen overdose, a condition causing severe oxidative mitochondrial damages and liver injury. Mitochondrial spheroids could undergo a maturation process by interactions with acidic compartments. The formation of this new structure required reactive oxygen species and mitofusins. Parkin suppressed these mitochondrial dynamics by promoting mitofusin degradation. Consistently, genetic deletion of mitofusins without concomitant expression of Parkin was sufficient to prevent mitochondrial spheroid formation and resumed mitophagy. Mitochondrial spheroid formation and mitophagy could represent different strategies of mitochondrial homeostatic response to oxidative stress and are reciprocally regulated by mitofusins and Parkin.

Original languageEnglish (US)
Pages (from-to)42379-42388
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number50
DOIs
StatePublished - Dec 7 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ding, W. X., Guo, F., Ni, H. M., Bockus, A., Manley, S., Stolz, D. B., Eskelinen, E. L., Jaeschke, H., & Yin, X. M. (2012). Parkin and mitofusins reciprocally regulate mitophagy and mitochondrial spheroid formation. Journal of Biological Chemistry, 287(50), 42379-42388. https://doi.org/10.1074/jbc.M112.413682