A, Schematic representation of the redistribution of IPS-1 induced by viral infection. In uninfected cells, IPS-1 is evenly distributed in all mitochondria (left). In infected cells, foci of viral nucleoprotein form, which are surrounded by redistributed IPS-1 and mitochondria (right). B, A model for the redistribution of IPS-1 mediated by mitochondrial organization. Initially, IPS-1 is distributed evenly in mitochondria (left). Viruses replicate in restricted compartments in the cells, viral RNA accumulates, and then RIG-I re-localizes to these compartments. Viral RNA induces a conformational change of RIG-I, and results in mitochondria expressing accumulated IPS-1- around the RIG-I foci. IPS-1 may be redistributed, resulting in a local accumulation of IPS-1 on a mitochondrion (left). IPS-I may further segregate due to mitochondrial reorganization by fusion and fission (right). Local accumulation of IPS-1 may further recruit adaptors and protein kinases to activate antiviral signaling.