Autophagosomal Content Profiling as a Tool to Dissect the Contribution of Autophagy to Proteostasis Christian Behrends Munich Cluster for Systems Neurology, Medical Faculty, Ludwig-Maximilian-Universität München, Munich, Germany
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 non-selective 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. Knowing the identities of autophagosomal substrates is particularly important to understand the functional consequences of altered autophagy activity in pathological conditions such as cancer or neurodegenerative disorders. To start addressing this issue, we combined proximity labeling with quantitative proteomics to systematically map the protein inventory of autophagosomes. Using this strategy, we recently uncovered a basal, housekeeping mitophagy pathway that involves piece-meal degradation of mitochondrial proteins in a LC3C- and p62- dependent manner and which contributes to mitochondrial homeostasis maintenance when cells rely on oxidative phosphorylation.
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