Mitochondria: central regulator of inflammatory pathways
Chronic inflammation is a major factor contributing to the origin of many cancer types, although specific
mechanisms of this association and its role in providing a survival advantage to tumor cells are not well
understood. Mitochondria are emerging as a central regulator of inflammatory pathways in addition to its
role in energy metabolism, maintaining calcium homeostasis and cell death. Mitochondria function as critical
signaling platform for assembly and relay of innate immune signaling as well as maintain cell bioenergetic
status. The reports from our lab strongly suggests that mitochondria localized protein such as MAVS, MITA
and NLRX1 forms novel signallosomes at the mitochondria and regulate NF-κB and type-1 interferon
pathways and mitochondrial function. These mitochondrial proteins further regulate the crosstalk of between
innate immune signaling and basic mitochondrial function to dictate cell survival and production of
inflammatory mediators such as TNF-α. We provided evidences for the first time that NLRX1 and MITA
function as novel tumor suppressors in regulating tumor cell survival and proliferation using human breast
cancer cell line as model system.