Phosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth

Selective autophagy can be mediated via receptor molecules that link specific cargoes to the autophagosomal membranes decorated by ubiquitin-like LC3 (microtubule-associated protein light chain 3) modifiers. Although several autophagy receptors have been identified, little is known about mechanisms controlling their functions in vivo. Here, we found that phosphorylation of an autophagy receptor, optineurin, promoted selective autophagy of ubiquitin-coated cytosolic Salmonella enterica. The protein kinase TBK1 (TANK binding kinase 1) phosphorylated optineurin on serine 177, enhancing LC3 binding affinity and autophagic clearance of cytosolic Salmonella. Conversely, ubiquitin- or LC3-binding optineurin mutants and silencing of optineurin or TBK1 impaired Salmonella autophagy resulting in increased intracellular bacterial proliferation. We propose that phosphorylation of autophagy receptors might be a general mechanism for regulation of cargo-selective autophagy.