TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation

Michael A Mandell, Ashish Jain, Suresh Kumar, Moriah J Castleman, Tahira Anwar, Eeva-Liisa Eskelinen, Terje Johansen, Rytis Prerekis, Vojo Deretic

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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.
Original languageEnglish
JournalJournal of Cell Science
Volume129
Pages (from-to)3562-3573
ISSN0021-9533
DOIs
Publication statusPublished - 1 Oct 2016
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology
  • HIV
  • Mcl-1
  • midbody
  • selective autophagy
  • tripartite motif

Projects

Cite this

Mandell, M. A., Jain, A., Kumar, S., Castleman, M. J., Anwar, T., Eskelinen, E-L., Johansen, T., Prerekis, R., & Deretic, V. (2016). TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation. Journal of Cell Science, 129, 3562-3573. https://doi.org/10.1242/jcs.190017