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

73 Citations (Scopus)

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

Fingerprint

Mitochondrial Degradation
Liver
Mitochondrial Dynamics
Mitochondria
Oxidative stress
Acetaminophen
Quality control
Reactive Oxygen Species
Autophagy
Degradation
Quality Control
Oxidative Stress
Homeostasis
Wounds and Injuries
mesoxalonitrile
carbonyl 3-chlorophenylhydrazone

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Parkin and mitofusins reciprocally regulate mitophagy and mitochondrial spheroid formation. / Ding, Wen Xing; Guo, Fengli; Ni, Hong Min; Bockus, Abigail; Manley, Sharon; Stolz, Donna B.; Eskelinen, Eeva Liisa; Jaeschke, Hartmut; Yin, Xiao-Ming.

In: Journal of Biological Chemistry, Vol. 287, No. 50, 07.12.2012, p. 42379-42388.

Research output: Contribution to journalArticle

Ding, WX, Guo, F, Ni, HM, Bockus, A, Manley, S, Stolz, DB, Eskelinen, EL, Jaeschke, H & Yin, X-M 2012, 'Parkin and mitofusins reciprocally regulate mitophagy and mitochondrial spheroid formation', Journal of Biological Chemistry, vol. 287, no. 50, pp. 42379-42388. https://doi.org/10.1074/jbc.M112.413682
Ding, Wen Xing ; Guo, Fengli ; Ni, Hong Min ; Bockus, Abigail ; Manley, Sharon ; Stolz, Donna B. ; Eskelinen, Eeva Liisa ; Jaeschke, Hartmut ; Yin, Xiao-Ming. / Parkin and mitofusins reciprocally regulate mitophagy and mitochondrial spheroid formation. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 50. pp. 42379-42388.
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