The essential role of mitochondrial dynamics in antiviral immunity

Figures

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  Fig. 1. Mitochondrial dynamics in viral infections. Under normal conditions, mitochondria display tubular morphology. Viral infection-induced stress causes mitochondrial damage. Asymmetric mitochondrial fission facilitates the segregation of the damaged mitochondria from the healthy ones, which are subsequently removed by mitophagy. The remaining healthy mitochondria fuse back into the tubular mitochondrial network. In this way, mitochondria maintain homeostasis and determine cell fate. During infection, viruses are able to modulate functions of cellular factors influencing mitochondrial dynamics (e.g., Drp1, Mfn, and OPA1) shifting mitochondrial dynamics towards either fission (mitochondrial fragmentation) or fusion (mitochondrial elongation) in favor of viral replication and propagation by either dampening innate immune signaling or by maintaining cell viability.

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  Fig. 2. Process of mitophagy through PINK1 and Parkin pathway. In healthy mitochondria, PINK1 (a mitochondrial serine/threonine protein kinase) is imported rapidly to IMM and subsequently degraded by mitochondrial proteases and proteasome. During viral infection, virus-induced stress triggers mitochondrial depolarization leading to reduced import of PINK1 to IMM, thereby resulting in the stabilization and activation of PINK1. Activated PINK1 initiates selective tagging of damaged mitochondria by phosphorylation of both ubiquitin and Parkin. Activated Parkin builds up ubiquitin chains, which are, in turn, phosphorylated by PINK1 amplifying the signal. The damaged mitochondria tagged with the unique signature of phospho-ubiquitin via PINK1 and Parkin activities are identified by the mitophagy receptors, which interact with LC3. This formation brings the autophagy machinery towards the damaged mitochondria for their subsequent engulfment within the expanding phagophore, resulting in the formation of mitophagosome.