Abstract
Mitochondria are dynamic organelles involved in numerous physiological functions. Beyond their function in ATP production, mitochondria regulate cell death, reactive oxygen species (ROS) generation, immunity and metabolism. Mitochondria also play a key role in the buffering of cytosolic calcium, and calcium transported into the matrix regulates mitochondrial metabolism. Recently, the identification of the mitochondrial calcium uniporter (MCU) and associated regulators has allowed the characterization of new physiological roles for calcium in both mitochondrial and cellular homeostasis. Indeed, recent work has highlighted the importance of mitochondrial calcium homeostasis in regulating cell migration. Cell migration is a property common to all metazoans and is critical to embryogenesis, cancer progression, wound-healing and immune surveillance. Previous work has established that cytoplasmic calcium is a key regulator of cell migration, as oscillations in cytosolic calcium activate cytoskeletal remodelling, actin contraction and focal adhesion (FA) turnover necessary for cell movement. Recent work using animal models and in cellulo experiments to genetically modulate MCU and partners have shed new light on the role of mitochondrial calcium dynamics in cytoskeletal remodelling through the modulation of ATP and ROS production, as well as intracellular calcium signalling. This review focuses on MCU and its regulators in cell migration during physiological and pathophysiological processes including development and cancer. We also present hypotheses to explain the molecular mechanisms by which MCU may regulate mitochondrial dynamics and motility to drive cell migration.
Highlights
Mitochondria are highly dynamic organelles that constantly undergo fusion and fission events to adapt their shape to the physiological needs of the cell
Loss of mitochondrial calcium uniporter (MCU) resulted in the inhibition of mitochondrial reactive oxygen species (ROS) production, which led to a reduction in the expression of the hypoxia induced factor 1a (HIF1a) transcription factor
Of the role of MCU in cancer cell migration, different studies have highlighted the role of mitochondrial Ca2þ homeostasis in immune cell polarization and chemotaxis [127,128]
Summary
Mitochondria are highly dynamic organelles that constantly undergo fusion and fission events to adapt their shape to the physiological needs of the cell. Mitochondrial plasticity allows their trafficking along the microtubules resulting in their strategic partitioning within the cell, which is crucial to ensure specialized functions such as immunity [1] and cell migration [2]. Transient contacts between ER and mitochondria are essential for a number of processes including autophagy, mitochondrial motility, lipid and calcium (Ca2þ) fluxes and mitochondrial division [3,4]. We will discuss the intimate connection between mitochondrial Ca2þ homeostasis and mitochondria dynamics/motility during this process
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