Mitochondrial quality control mediated by PINK1 and PRKN: links to iron metabolism and tumor immunity

Rui Kang, Yangchun Xie, Herbert J. Zeh, Daniel J. Klionsky, Daolin Tang

Research output: Contribution to journalComment/debate

2 Citations (Scopus)

Abstract

Mitochondrial quality control is an essential process required to maintain cellular homeostasis and functions. Mutations of PINK1 and PRKN/PARK2 contribute to the risk of Parkinson disease. Our recent findings indicate that depletion of Pink1 and Prkn promotes pancreatic tumorigenesis in KRAS-driven engineered mouse models. Mechanistically, PINK1- and PRKN-mediated autophagic degradation of mitochondrial iron importers (e.g., SLC25A37 and SLC25A28) suppresses pancreatic tumor growth by attenuating mitochondrial iron accumulation, inflammasome activation, HMGB1 release, and subsequent immune checkpoint expression. Consequently, pharmacological or genetic inhibition of mitochondrial iron-dependent signals prolongs animal survival and reverses pancreatic tumor phenotype in vivo. Thus, PINK1- and PRKN-mediated immunometabolism provides new insights into the tumor microenvironment and could be a suitable target for new pancreatic cancer treatments.

Original languageEnglish (US)
Pages (from-to)172-173
Number of pages2
JournalAutophagy
Volume15
Issue number1
DOIs
StatePublished - Jan 2 2019

Fingerprint

Quality Control
Immunity
Iron
Inflammasomes
HMGB1 Protein
Neoplasms
Tumor Microenvironment
Pancreatic Neoplasms
Parkinson Disease
Carcinogenesis
Homeostasis
Pharmacology
Phenotype
Mutation
Growth

Keywords

  • Cancer
  • CD274
  • HMGB1
  • immunometabolism
  • iron
  • PINK1
  • PRKN
  • SLC25A28
  • SLC25A37

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Mitochondrial quality control mediated by PINK1 and PRKN : links to iron metabolism and tumor immunity. / Kang, Rui; Xie, Yangchun; Zeh, Herbert J.; Klionsky, Daniel J.; Tang, Daolin.

In: Autophagy, Vol. 15, No. 1, 02.01.2019, p. 172-173.

Research output: Contribution to journalComment/debate

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AU - Tang, Daolin

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