Table 2.

List of autophagy receptors involved in xenophagy and their functions.

Receptors	Process	Tag	Role	References
TAX1BP1	Xenophagy Mitophagy	Ub	TAX1BP1, modulated by LAMTOR1-LAMTOR2 complex, is recruited to ubiquitinated bacteria along with MYO6 (myosin VI) and helps in elimination of pathogens by xenophagy.	[69,107–109]
CALCOCO2	Mitophagy Xenophagy	LGALS8, Ub	Targets pathogens to autophagosomes mediated by interaction with LC3C or LGALS8. It also promotes the maturation of autophagosomes by interacting with LC3A, LC3B, and/or GABARAPL2. Moreover, along with MTPAP (mitochondrial poly(A) polymerase) it forms autophagy receptor complex for enhanced removal of damaged mitochondria via mitophagy.	[110,111]
OPTN	Autophagy Xenophagy Aggrephagy Mitophagy	Ub	OPTN acts as an autophagic receptor for the removal of polyubiquitinated substrates. Enhanced binding to Ub chains after phosphorylation by TBK1 promotes mitophagy. OPTN also mediates the degradation of inclusion bodies in Ub-dependent manner. This receptor is also critical for autophagic host defense against intracellular infections.	[112–114]
SQSTM1	Autophagy Xenophagy Mitophagy Aggrephagy Lipophagy Pexophagy	Ub	SQSTM1 is involved in LC3-mediated linking of ubiquitinated protein aggregates to autophagic machinery. Phosphorylated SQSTM1 promotes Ub conjugation during xenophagy and is important for controlling cytosolic bacteria. Ubiquitination of mitochondrial proteins requires SQSTM1 during mitophagy. It is also involved in organelle quality control like pexophagy as well as lipophagy.	[115,116,117]
NBR1	Mitophagy Xenophagy Aggrephagy Pexophagy	Ub	NBR1 is a specific receptor involved in pexophagy. It also acts as a receptor for autophagosomal degradation of ubiquitinated targets but is dispensable for mitophagy. NBR1 binds bacterial pathogens and viral particles to mediate their xenophagic degradation.	[81,118,119]

The autophagy receptors TAX1BP1, CALCOCO2, OPTN, SQSTM1, and NBR1, are involved in the xenophagic clearance of Ub-tagged intracellular cytosolic bacteria. The functions of SQSTM1 in xenophagy and other processes such as mitophagy, aggrephagy, lipophagy, and pexophagy are well-established. The function and roles of other autophagy receptors are emerging now in xenophagy and other “phagy.” Importantly, in autophagic clearance of invading pathogens, these receptors execute non-redundant functions, although they perform redundant functions in other processes such as aggrephagy.