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Oncotarget. 2015 Aug 28;6(25):20754-72.

Mitochondria, calcium, and tumor suppressor Fus1: At the crossroad of cancer, inflammation, and autoimmunity.

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Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, Tennessee, United States.
Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University, Nashville, Tennessee, United States.
Department of Surgery, Division of Otolaryngology, Yale School of Medicine, New Haven, Connecticut, United States.
Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, United States.
Department of Pathology, Yale School of Medicine, New Haven, Connecticut, United States.


Mitochondria present a unique set of key intracellular functions such as ATP synthesis, production of reactive oxygen species (ROS) and Ca2+ buffering. Mitochondria both encode and decode Ca2+ signals and these interrelated functions have a direct impact on cell signaling and metabolism. High proliferative potential is a key energy-demanding feature shared by cancer cells and activated T lymphocytes. Switch of a metabolic state mediated by alterations in mitochondrial homeostasis plays a fundamental role in maintenance of the proliferative state. Recent studies show that tumor suppressors have the ability to affect mitochondrial homeostasis controlling both cancer and autoimmunity. Herein, we discuss established and putative mechanisms of calcium-dependent regulation of both T cell and tumor cell activities. We use the mitochondrial protein Fus1 as a case of tumor suppressor that controls immune response and tumor growth via maintenance of mitochondrial homeostasis. We focus on the regulation of mitochondrial Ca2+ handling as a key function of Fus1 and highlight the mechanisms of a crosstalk between Ca2+ accumulation and mitochondrial homeostasis. Given the important role of Ca2+ signaling, mitochondrial Ca2+ transport and ROS production in the activation of NFAT and NF-κB transcription factors, we outline the importance of Fus1 activities in this context.


Fus1/Tusc2; autoimmunity; calcium; inflammation; mitochondria; tumor suppressor

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