Mitochondrial calcium signaling in the brain and its modulation by neurotropic viruses

Calcium (Ca²⁺) plays fundamental and diverse roles in brain cells as a second messenger of many signaling pathways. Given the high energy demand in the brain and the generally non-regenerative state of neurons, the role of brain mitochondrial calcium [Ca²⁺]_m in particular, in regulating ATP generation and determination of cell fate by initiation or inhibition of programmed cell death (PCD) becomes critical. Since [Ca²⁺]_m signaling has a central role in brain physiology, it represents an ideal target for viruses to hijack the Ca²⁺ machinery to favor their own persistence, replication and/or dissemination by modulating cell death. This review discusses the ways by which neurotropic viruses are known to exploit the [Ca²⁺]_m signaling of their host cells to regulate cell death in the brain, particularly in neurons. We hope our review will highlight the importance of [Ca²⁺]_m handling in the virus-infected brain and stimulate further studies towards exploring novel [Ca²⁺]_m related therapeutic strategies for viral effects on the brain.