Abstract
The Ca2+-binding protein parvalbumin (PV) and mitochondria play important roles in Ca2+ signaling, buffering and sequestration. Antagonistic regulation of PV and mitochondrial volume is observed in in vitro and in vivo model systems. Changes in mitochondrial morphology, mitochondrial volume and dynamics (fusion, fission, mitophagy) resulting from modulation of PV were investigated in MDCK epithelial cells with stable overexpression/downregulation of PV. Increased PV levels resulted in smaller, roundish cells and shorter mitochondria, the latter phenomenon related to reduced fusion rates and decreased expression of genes involved in mitochondrial fusion. PV-overexpressing cells displayed increased mitophagy, a likely cause for the decreased mitochondrial volumes and the smaller overall cell size. Cells showed lower mobility in vitro, paralleled by reduced protrusions. Constitutive PV down-regulation in PV-overexpressing cells reverted mitochondrial morphology and fractional volume to the state present in control MDCK cells, resulting from increased mitochondrial movement and augmented fusion rates. PV-modulated, bi-directional and reversible mitochondrial dynamics are key to regulation of mitochondrial volume.
Highlights
Parvalbumin (PV) is a cytosolic C a2+-binding protein of the large EF-hand protein family, implicated in intracellular Ca2+ regulation and trafficking [12, 75, 79]
The PV concentration observed in PV-Madin–Darby canine kidney (MDCK) cells falls well within the range of PV concentrations found in neurons (e.g. Purkinje cells or cerebellar interneurons) ranging from 50 to 1500 μM depending on cell type and species [22, 33, 75]
An intricate interplay between PV and mitochondria has been observed in excitable and non-excitable cells before, entailing a clearly antagonistic mechanism; up-regulation of PV expression leads to a decrease in mitochondrial volume and vice versa by a likely homeostatic mechanism [31, 41]. Ca2+ buffering by PV and C a2+
Summary
Parvalbumin (PV) is a cytosolic C a2+-binding protein of the large EF-hand protein family, implicated in intracellular Ca2+ regulation and trafficking [12, 75, 79]. PV is highly expressed in fast-twitch muscles and distinct neuron subpopulations, where PV plays an important role in Ca2+ signaling, e.g. by increasing the relaxation rate of fast-twitch muscles [78] or by modulation of short-term synaptic plasticity in PV-expressing neurons [11, 64]. It is expressed in mouse renal epithelial cells of the distal convoluted tubule, where PV is suggested to function as an intracellular C a2+ shuttle involved in transcellular Ca2+ resorption [41]. Alteration of PV expression levels does not affect levels of other co-expressed EF-hand Ca2+-binding proteins
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
