Abstract:
:Mitochondrial translocation of ceramides triggers Bax-dependent apoptosis. To elucidate how ceramides activate Bax and commit cells to death, we developed a switchable version of the ceramide transfer protein CERT, sCERT. Upon its drug-induced recruitment to mitochondria, sCERT retains the ability to bind VAP proteins in the ER and catalyzes mitochondrial import of externally added fluorescent ceramides. Mitochondrial recruitment of sCERT also triggers mitochondrial translocation of Bax. The ability of mitochondria-bound sCERT to mediate ceramide import and Bax translocation requires both its START domain and ongoing ceramide biosynthesis. These data extend our previous finding that mistargeting of ER ceramides to mitochondria specifically activates Bax and establish sCERT as a novel tool to dissect the underlying mechanism in a time-resolved manner.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Jain A,Dadsena S,Holthuis JCMdoi
10.1002/1873-3468.13956subject
Has Abstractpub_date
2020-11-01 00:00:00pages
3739-3750issue
22eissn
0014-5793issn
1873-3468journal_volume
594pub_type
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