Autophagosomal Content Profiling Reveals an LC3C-Dependent Piecemeal Mitophagy Pathway

François Le Guerroué, Franziska Eck, Jennifer Jung, Tatjana Starzetz, Michel Mittelbronn, Manuel Kaulich, Christian Behrends*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

88 Citations (Scopus)


Autophagy allows the degradation of cytosolic endogenous and exogenous material in the lysosome. Substrates are engulfed by double-membrane vesicles, coined autophagosomes, which subsequently fuse with lysosomes. Depending on the involvement of specific receptor proteins, autophagy occurs in a selective or nonselective manner. While this process is well understood at the level of bulky cargo such as mitochondria and bacteria, we know very little about individual proteins and protein complexes that are engulfed and degraded by autophagy. In contrast to the critical role of autophagy in balancing proteostasis, our current knowledge of the autophagic degradome is very limited. Here, we combined proximity labeling with quantitative proteomics to systematically map the protein inventory of autophagosomes. Using this strategy, we uncovered a basal, housekeeping mitophagy pathway that involves piecemeal degradation of mitochondrial proteins in a LC3C- and p62-dependent manner and contributes to mitochondrial homeostasis maintenance when cells rely on oxidative phosphorylation. In this study, Le Guerroué et al. employed proximity-proteomics-based autophagosome content profiling to identify a role for LC3C in maintaining basal mitochondrial homeostasis. Selected mitochondrial proteins, including MTX1, were targeted by LC3C and p62 through a piecemeal mitophagy pathway.

Original languageEnglish
Pages (from-to)786-796.e6
JournalMolecular Cell
Issue number4
Publication statusPublished - 16 Nov 2017


  • APEX2
  • LC3C
  • MTX1
  • SQSTM1
  • autophagosomes
  • enzyme-based proximity labeling
  • human ATG8 family
  • mitophagy
  • p62
  • piecemeal degradation


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