Phosphorylation of mitochondrial matrix proteins regulates their selective mitophagic degradation

Panagiota Kolitsida, Jianwen Zhou, Michal Rackiewicz, Vladimir Nolic, Jörn Dengjel, Hagai Abeliovich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Mitophagy is an important quality-control mechanism in eukaryotic cells, and defects in mitophagy correlate with aging phenomena and neurodegenerative disorders. It is known that different mitochondrial matrix proteins undergo mitophagy with very different rates but, to date, the mechanism underlying this selectivity at the individual protein level has remained obscure. We now present evidence indicating that protein phosphorylation within the mitochondrial matrix plays a mechanistic role in regulating selective mitophagic degradation in yeast via involvement of the Aup1 mitochondrial protein phosphatase, as well as 2 known matrix-localized protein kinases, Pkp1 and Pkp2. By focusing on a specific matrix phosphoprotein reporter, we also demonstrate that phospho-mimetic and nonphosphorylatable point mutations at known phosphosites in the reporter increased or decreased its tendency to undergo mitophagy. Finally, we show that phosphorylation of the reporter protein is dynamically regulated during mitophagy in an Aup1-dependent manner. Our results indicate that structural determinants on a mitochondrial matrix protein can govern its mitophagic fate, and that protein phosphorylation regulates these determinants.

Original languageAmerican English
Pages (from-to)20517-20527
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
StatePublished - 8 Oct 2019

Bibliographical note

Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.


  • Autophagy
  • Mitophagy
  • Phosphatase
  • Protein phosphorylation
  • Saccharomyces cerevisiae


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