Mitochondrial Ca2+ as a key regulator of cell life and death

The role of mitochondria in apoptosis

“…2+ is one of the key regulators of not only cell survival but also cell death in response to a variety of cellular signals (42). The pro-apoptotic effects of Ca 2+ are mediated by a diverse range of Ca 2+ sensitive factors that are compartmentalized in various intracellular organelles including the ER, cytoplasm, and mitochondria (43).…”

Adrenergic Signaling Regulates Mitochondrial Ca2+ Uptake Through Pyk2-Dependent Tyrosine Phosphorylation of the Mitochondrial Ca2+ Uniporter

“…2+ homeostasis determines numerous cell functions, including energy metabolism, reactive oxygen species (ROS) generation, spatiotemporal dynamics of Ca 2+ signaling, cell growth/development, and death (19,24,56,57). The mitochondrial Ca 2+ uniporter (mtCU), which is inhibited by lanthanides and ruthenium red (26), is the primary mechanism for mitochondrial Ca 2+ influx in all cell types (8).…”

Properties of Ca2+ Transport in Mitochondria of Drosophila melanogaster

“…Consequently, when local cytoplasmic free Ca 2ϩ levels rise, mitochondria rapidly accumulate cytoplasmic Ca 2ϩ and then gradually release it as normal cytoplasmic levels are restored, amplifying and sustaining signals arising from elevation of cytoplasmic Ca 2ϩ , as well as protecting cells and neurons against transient elevation in intracellular Ca 2ϩ during periods of hyperactivity (1,5,6). As a result, the mechanisms controlling cellular and mitochondrial Ca 2ϩ homeostasis, metabolism, and bioenergetics must function as a tightly integrated system within the overall cellular Ca 2ϩ homeostatic network (2,(7)(8)(9). The pathways responsible for mitochondrial Ca 2ϩ uptake and release have been intensely studied on a functional level for Ͼ50 years.…”