Selective ubiquitination in lysophagy, lysosome maintenance, and lysosomal disorders
Ubiquitination has been implicated as a key signal for the selective degradation of substrates through autophagy. We have previously discovered that damaged lysosomes undergo selective ubiquitination, recruit autophagic adaptors, and are eventually turned over through that autophagic pathway (termed lysophagy). It however remains unknown what ubiquitin ligases mediate this degradation pathway. With the help of this grant and others we attempted to develop an APEX-based strategy to identify the ubiquitin ligases involved. Using this strategy we identified a panel of candidates that may be responsible for lysophagy. These candidates will be subjected to future testing for complete understanding of the lysophagy pathway.