CaM kinase Iα-induced phosphorylation of Drp1 regulates mitochondrial morphology

Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in...

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Bibliographic Details
Published in:The Journal of cell biology 2008-08, Vol.182 (3), p.573-585
Main Authors: Han, Xiao-Jian, Lu, Yun-Fei, Li, Shun-Ai, Kaitsuka, Taku, Sato, Yasufumi, Tomizawa, Kazuhito, Nairn, Angus C, Takei, Kohji, Matsui, Hideki, Matsushita, Masayuki
Format: Article
Language:English
Subjects:
Animals
Calcium Channels - metabolism
Calcium Signaling - drug effects
Calcium-Calmodulin-Dependent Protein Kinase Type 1 - metabolism
Dynamins - metabolism
HeLa Cells
Humans
Intracellular Space - drug effects
Membrane Proteins - metabolism
Mitochondria - drug effects
Mitochondria - enzymology
Mitochondria - metabolism
Mitochondria - ultrastructure
Mitochondrial Proteins - metabolism
Neurons - cytology
Neurons - drug effects
Neurons - enzymology
Phosphorylation - drug effects
Potassium - pharmacology
Protein Binding - drug effects
Protein Transport - drug effects
Rats
Rats, Wistar
Recombinant Proteins - metabolism
Serine - metabolism
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Summary:Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in neurons. Using time-lapse imaging, we find that Ca²⁺ influx through voltage-dependent Ca²⁺ channels (VDCCs) causes a rapid halt in mitochondrial movement and induces mitochondrial fission. VDCC-associated Ca²⁺ signaling stimulates phosphorylation of dynamin-related protein 1 (Drp1) at serine 600 via activation of Ca²⁺/calmodulin-dependent protein kinase Iα (CaMKIα). In neurons and HeLa cells, phosphorylation of Drp1 at serine 600 is associated with an increase in Drp1 translocation to mitochondria, whereas in vitro, phosphorylation of Drp1 results in an increase in its affinity for Fis1. CaMKIα is a widely expressed protein kinase, suggesting that Ca²⁺ is likely to be functionally important in the control of mitochondrial dynamics through regulation of Drp1 phosphorylation in neurons and other cell types.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200802164