TRIM proteins contribute to selective autophagy, a process whereby cells target specific cargo for autophagic degradation. In a previously reported screen, TRIM17 acted as a prominent inhibitor of bulk autophagy, unlike the majority of TRIMs, which had positive roles. Nevertheless, TRIM17 showed biochemical hallmarks of autophagy-inducing TRIMs. To explain this paradox, here, we investigated how TRIM17 inhibits selective autophagic degradation of a subset of targets while promoting degradation of others. We traced the inhibitory function of TRIM17 to its actions on the anti-autophagy protein Mcl-1, which associates with and inactivates Beclin 1. TRIM17 expression stabilized Mcl-1–Beclin-1 complexes. Despite its ability to inhibit certain types of selective autophagy, TRIM17 promoted the removal of midbodies, remnants of the cell division machinery that are known autophagy targets. The selective loss of anti-autophagy Mcl-1 from TRIM17–Beclin-1 complexes at midbodies correlated with the ability of TRIM17 to promote midbody removal. This study further expands the roles of TRIMs in regulating selective autophagy by showing that a single TRIM can, depending upon a target, either positively or negatively regulate autophagy.
The authors declare no competing or financial interests.
M.A.M., T.A., S.K., M.J.C., and A.J. performed experiments and analyzed the data. M.A.M., R.P., E.L.-E., T.J., and V.D. designed and supervised experiments. M.A.M. and V.D. wrote the manuscript.
This work was supported by the National Institutes of Health [grant numbers AI042999 and AI111935 to V.D.]. E.L.-E. and T.A. were supported by the Suomen Akatemia (Academy of Finland) and the Magnus Ehrnroothin Säätiö (Magnus Ehrnrooth Foundation). Deposited in PMC for release after 12 months.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.190017.supplemental
- Received March 31, 2016.
- Accepted August 13, 2016.
- © 2016. Published by The Company of Biologists Ltd