Mitochondrial Calcium Influx is Determined by Multiple Protein Components Including SLC25A23 and MICU1 [article]

(:Unkn) Unknown, Madesh Muniswamy, University, My
2020
Ca2+ control mechanisms employed by the cell at the plasma membrane include receptor operated, voltage-sensitive, and store operated channels for Ca2+ import. Upon entry into the cytosol, Ca2+ is sequestered by Ca2+ binding proteins, the endoplasmic reticulum (ER), or by mitochondria. The largest Ca2+ store in the cell is the ER where Ca2+ levels approach millimolar levels. The ER regulates cytosolic Ca2+ homeostasis by using Ca2+ binding proteins, the SERCA pump, second messenger Ca2+ release
more » ... enger Ca2+ release upon IP3 receptor activation, and Ca2+-induced Ca2+ release by ryanodine receptors. Basal cytosolic Ca2+ levels are maintained at around 100nM. The mitochondria begins clearing GPRC-depended cytosolic Ca2+elevation after a short time delay during which the cytosolic Ca2+ concentration exceeds 3M. Then, the mitochondria sacrifices a portion of its membrane potential to drive Ca2+ influx across the mitochondrial inner membrane into the matrix. The membrane potential of the mitochondria is created in part by the electron transport, which while transferring electrons, ejects protons from the matrix to the inner membrane space. The rapid mitochondrial Ca2+ uptake decreases mitochondrial membrane potential thus reducing or fully collapsing the mitochondria's ability to generate ATP. This uncoupling of the electron transport chain results in ROS production and decreased cell survival. Mitochondria provide the body with energy that allows a heart to beat, a brain to store memories, and fuels locomotive function. As a stand-alone energy generator, the mitochondria would be interesting, but not dynamic. The dynamic flow of information to the mitochondria through Ca2+ signaling with all the components of symbiotic precision is a true biological phenomenon. In the mitochondria, a complex Ca2+ buffering system of channels, pores, and exchangers directly affects the conversion of chemical potential to ATP. Recent, discoveries of the Ca2+ uniporter (MCU) and other system components have provided the tools to tackle levels of mitochondrio [...]
doi:10.34944/dspace/2992 fatcat:4s6d45h4kvbflj4wvnph5rv7pa