The Role of Autophagy and Autophagy Receptor NDP52 in Microbial Infections

Abstract

Autophagy is a general protective mechanism for maintaining homeostasis in eukaryotic cells, regulating cellular metabolism, and promoting cell survival by degrading and recycling cellular components under stress conditions. The degradation pathway that is mediated by autophagy receptors is called selective autophagy, also named as xenophagy. Autophagy receptor NDP52 acts as a ‘bridge’ between autophagy and the ubiquitin-proteasome system, and it also plays an important role in the process of selective autophagy. Pathogenic microbial infections cause various diseases in both humans and animals, posing a great threat to public health. Increasing evidence has revealed that autophagy and autophagy receptors are involved in the life cycle of pathogenic microbial infections. The interaction between autophagy receptor and pathogenic microorganism not only affects the replication of these microorganisms in the host cell, but it also affects the host’s immune system. This review aims to discuss the effects of autophagy on pathogenic microbial infection and replication, and summarizes the mechanisms by which autophagy receptors interact with microorganisms. While considering the role of autophagy receptors in microbial infection, NDP52 might be a potential target for developing effective therapies to treat pathogenic microbial infections.

Crosstalk Between NDP52 and LUBAC in Innate Immune Responses, Cell Death, and Xenophagy

“…Human NDP52 consists of the SKIP carboxyl homology (SKICH), LC3-interacting region (LIR), coiled-coil, galectin-8 binding (GALBI), and C-terminal ubiquitin-binding zinc finger (UBZ) domains ( 17 , 19 ) ( Figure 1A ). The substitution of Asp439 by Arg (D439R) in the UBZ domain reportedly abolishes the ubiquitin-binding ( 31 ).…”

“…NDP52 is a multifunctional regulatory protein that predominantly works in selective autophagy ( 17 , 18 ). Although linear (de)ubiquitination is involved in the NDP52-mediated xenophagy of invading Salmonella ( 24 , 25 ), little is known about the crosstalk between NDP52 and LUBAC in innate immune responses.…”

Autophagy receptors as viral targets

“…In addition to binding myosin VI, T6BP/TAX1BP1 and CALCOCO2/NDP52 also bind each other and have been suggested to modulate cytokine signaling and membrane transport with actin filament organization and cell adhesion [ 47 ]. There are several recent studies on CALCOCO2/NDP52 that have revealed important molecular insights on its role as the recruiter of the early autophagic protein complexes to the cargo, initiating selective autophagy [ 48 – 50 ], and a recent review summarizes its role in microbial infections, including viruses [ 51 ]. CALCOCO2/NDP52 has a role in innate immunity through NFKB and type I IFN regulation, which can be another explanation for CSFV CALCOCO2/NDP52 targeting.…”

Immunosubunit β5i Knockout Suppresses Neovascularization and Restores Autophagy in Retinal Neovascularization by Targeting ATG5 for Degradation

“… 18 , 40 , 41 A previous report has shown that NDP52, an autophagy receptor, links autophagy and the UPS. 42 Rapamycin-induced autophagy promotes cell survival in the presence of proteasome inhibitors in vivo and in vitro. 43 , 44 Proteasome inhibition activates autophagy, with p62 acting as a bridge.…”