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.