TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct Autophagy in Endomembrane Damage Homeostasis

Publication date: Available online 29 September 2016
Source:Developmental Cell
Author(s): Santosh Chauhan, Suresh Kumar, Ashish Jain, Marisa Ponpuak, Michal H. Mudd, Tomonori Kimura, Seong Won Choi, Ryan Peters, Michael Mandell, Jack-Ansgar Bruun, Terje Johansen, Vojo Deretic
Selective autophagy performs an array of tasks to maintain intracellular homeostasis, sterility, and organellar and cellular functionality. The fidelity of these processes depends on precise target recognition and limited activation of the autophagy apparatus in a localized fashion. Here we describe cooperation in such processes between the TRIM family and Galectin family of proteins. TRIMs, which are E3 ubiquitin ligases, displayed propensity to associate with Galectins. One specific TRIM, TRIM16, interacted with Galectin-3 in a ULK1-dependent manner. TRIM16, through integration of Galectin- and ubiquitin-based processes, coordinated recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1, ULK1, and Beclin 1 in response to damaged endomembranes. TRIM16 affected mTOR, interacted with TFEB, and influenced TFEB's nuclear translocation. The cooperation between TRIM16 and Galectin-3 in targeting and activation of selective autophagy protects cells from lysosomal damage and Mycobacterium tuberculosis invasion.

Graphical abstract

Teaser

Selective autophagy contributes to intracellular homeostasis. Chauhan, Kumar, Jain, Ponpuak et al. show that TRIM family proteins, via interactions with Galectin proteins, recognize membrane damage and direct autophagic homeostasis of lysosomal and phagosomal organelles. They function by assembling core autophagy factors and influencing mTOR and TFEB activity.


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