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Mol Cell. 2017 Nov 16;68(4):786-796.e6. doi: 10.1016/j.molcel.2017.10.029.

Autophagosomal Content Profiling Reveals an LC3C-Dependent Piecemeal Mitophagy Pathway.

Author information

1
Institute of Biochemistry II, Medical School Goethe University, Frankfurt, Germany; Munich Cluster for Systems Neurology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.
2
Munich Cluster for Systems Neurology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany.
3
Institute of Biochemistry II, Medical School Goethe University, Frankfurt, Germany.
4
Neurological Institute (Edinger Institute), Goethe University, Frankfurt, Germany.
5
Neurological Institute (Edinger Institute), Goethe University, Frankfurt, Germany; Luxembourg Centre of Neuropathology (LCNP), Dudelange, Luxembourg; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg; NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH), Strassen, Luxembourg; Laboratorie National de Santè, Department of Pathology, Dudelange, Luxembourg.
6
Institute of Biochemistry II, Medical School Goethe University, Frankfurt, Germany; Munich Cluster for Systems Neurology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address: christian.behrends@mail03.med.uni-muenchen.de.

Abstract

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.

KEYWORDS:

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

PMID:
29149599
DOI:
10.1016/j.molcel.2017.10.029
[Indexed for MEDLINE]

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