Understanding the mechanisms of mitochondrial rewiring during viral infections

As intracellular parasites, viruses must hijack and often rewire organelles, signalling pathways and the bioenergetics machinery of the infected cell to replicate their genome, produce viral proteins and assemble new viral particles. Mitochondria are key eukaryotic organelles often referred to as the cell's powerhouse. They control many fundamental cellular processes, from metabolism and energy production to calcium homeostasis and programmed cell death. Importantly, mitochondrial membranes are also critical sites for the integration and amplification of antiviral innate immune responses. Overall, mitochondria are therefore both supporting the virus life cycle by sustaining energy production, metabolism and synthesis of macromolecules and part of the cell's first line of defence against viruses. This review summarizes recent findings on viral manipulations of mitochondria and their functions. We explore the evolving understanding of how mitochondrial dynamics is targeted to regulate innate immunity, evasion strategies used to avoid mitochondrial-associated mechanisms that impair replication and the role of mitochondrial functions such as generating reactive oxygen species or regulating the electron transport chain during infection. Overall, we provide a comprehensive view of how viruses modulate mitochondrial function to promote replication.