Abstract
Selective autophagy contributes to the wellbeing of eukaryotic cells by recycling cellular components, disposing damaged organelles, and removing pathogens, amongst others. Both the quality control process of selective mitochondrial autophagy (Mitophagy) and the defensive process of intracellular pathogen-engulfment (Xenophagy) are facilitated via protein assemblies which have shared molecules, a prime example being the Tank-Binding Kinase 1 (TBK1). TBK1 plays a central role in the immunity response driven by Xenophagy and was recently shown to be an amplifying mechanism in Mitophagy, bring to attention the potential cross talk between the two processes. Here we draw parallels between Xenophagy and Mitophagy, speculating on the inhibitory mechanisms of specific proteins (e.g., the 18 kDa protein TSPO), how the preferential sequestering toward one of the two pathways may undermine the other, and in this way impair cellular response to pathogens and cellular immunity. We believe that an in depth understanding of the commonalities may present an opportunity to design novel therapeutic strategies targeted at both the autonomous and non-autonomous processes of selective autophagy.
Highlights
Running comparative investigations on species-specific processes allows the comprehension of the underlying biological phenomena; better framing their general value and devising accurate strategies of intervention
The recent advancements on the molecular function of Tank-binding kinase 1 (TBK1) unveiled a role in mitophagy complementing the established one in Xenophagy (Thurston et al, 2009; Wild et al, 2011; Pilli et al, 2012) This has provided us with an opportunity to discuss values and dangers of a similar molecular co-sharing besides posing novel questions on core regulatory aspects of mammalian cells homeostasis in health and disease
When pathogens undergo recognition through pattern recognition receptors (PRRs) (Levine and Klionsky, 2004) whereby PRRs identify the pathogen associated molecular patterns (PAMPs). This initiates the immune signaling preceding the internalization of the pathogen and the activation of the autophagy machinery resulting in entrapment in autophagosomes once within the cytosol and subsequent autolysosomal degradation (Delgado et al, 2009; Oh and Lee, 2014)
Summary
Running comparative investigations on species-specific processes allows the comprehension of the underlying biological phenomena; better framing their general value and devising accurate strategies of intervention. Autophagy patrols the intracellular environment and can do so selectively by targeting either mitochondria (mitophagy) (Lemasters, 2005), protein aggregates (aggrephagy) (Lamark and Johansen, 2012), lipids (lipophagy) (Weidberg et al, 2009) or pathogens (xenophagy) (Levine, 2005) with new selective autophagy mechanisms being discovered continuously. These means of cellular quality control rely on molecular mechanism, which may be common between them and account for a subtle interplay to which little attention has been devoted. The recent advancements on the molecular function of Tank-binding kinase 1 (TBK1) unveiled a role in mitophagy complementing the established one in Xenophagy (Thurston et al, 2009; Wild et al, 2011; Pilli et al, 2012) This has provided us with an opportunity to discuss values and dangers of a similar molecular co-sharing besides posing novel questions on core regulatory aspects of mammalian cells homeostasis in health and disease
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