CaM kinase Iα-induced phosphorylation of Drp1 regulates mitochondrial morphology

Xiao Jian Han, Yun Fei Lu, Shun Ai Li, Taku Kaitsuka, Yasufumi Sato, Kazuhito Tomizawa, Angus C. Nairn, Kohji Takei, Hideki Matsui, Masayuki Matsushita

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271 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)573-585
Number of pages13
JournalJournal of Cell Biology
Volume182
Issue number3
DOIs
Publication statusPublished - Aug 11 2008

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Calcium-Calmodulin-Dependent Protein Kinase Type 1
Dynamins
Mitochondrial Dynamics
Phosphorylation
Proteins
Neurons
Serine
Mitochondria
Time-Lapse Imaging
Protein Transport
HeLa Cells
Organelles
Protein Kinases

ASJC Scopus subject areas

  • Cell Biology

Cite this

Han, X. J., Lu, Y. F., Li, S. A., Kaitsuka, T., Sato, Y., Tomizawa, K., ... Matsushita, M. (2008). CaM kinase Iα-induced phosphorylation of Drp1 regulates mitochondrial morphology. Journal of Cell Biology, 182(3), 573-585. https://doi.org/10.1083/jcb.200802164

CaM kinase Iα-induced phosphorylation of Drp1 regulates mitochondrial morphology. / Han, Xiao Jian; Lu, Yun Fei; Li, Shun Ai; Kaitsuka, Taku; Sato, Yasufumi; Tomizawa, Kazuhito; Nairn, Angus C.; Takei, Kohji; Matsui, Hideki; Matsushita, Masayuki.

In: Journal of Cell Biology, Vol. 182, No. 3, 11.08.2008, p. 573-585.

Research output: Contribution to journalArticle

Han, Xiao Jian ; Lu, Yun Fei ; Li, Shun Ai ; Kaitsuka, Taku ; Sato, Yasufumi ; Tomizawa, Kazuhito ; Nairn, Angus C. ; Takei, Kohji ; Matsui, Hideki ; Matsushita, Masayuki. / CaM kinase Iα-induced phosphorylation of Drp1 regulates mitochondrial morphology. In: Journal of Cell Biology. 2008 ; Vol. 182, No. 3. pp. 573-585.
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