Toward a new STATe: The role of STATs in mitochondrial function

• Recent studies have demonstrated a pool of STAT3 resides in the mitochondria where it has actions distinct from its role as a nuclear transcription factor.
• Mitochondrial STAT3 has important functional consequences in the areas of metabolism, cancer, and response to cell stress.
• Other STATs besides STAT3 have also been shown in the mitochondria.
• The emerging role of mitochondrial STATs suggests a much broader cellular function than their actions as a transcription factor.

Signal Transducers and Activators of Transcription (STATs) have been studied extensively and have been associated with virtually every biochemical pathway. Until recently, however, they were thought to exert these effects solely as a nuclear transcription factor. The finding that STAT3 localizes to the mitochondria and modulates respiration has opened up a new avenue through which STATs may regulate the cell. Recently, other members of the STAT family (STAT1, STAT2, STAT5, and STAT6) have also been shown to be present in the mitochondria. Coordinate regulation at the nucleus and mitochondria by these proteins places them in a unique position to drive cellular processes to achieve a specific response. This review summarizes recent findings that have led to our current understanding of how STATs influence mitochondrial function in health and disease.