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Published online
doi:10.1083/jcb.1823iti4
The Journal of Cell Biology, Vol. 182, No. 3, 413-
The Rockefeller University Press, 0021-9525 $30.00
© Robinson
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Mitochondria split with a calcium hit



Figure 1
Mitochondrial fragmentation in response to K+ stimulation (left) is blocked by preventing phosphorylation of Drp1 (right).

An influx of calcium into neurons causes mitochondrial fission, according to Han et al.

To respond to changing cellular needs, mitochondria move, fuse together, or undergo fission. Han et al. now reveal some of the proteins and signals that regulate fission in neurons.

The authors tested mitochondrial responses to an increase in potassium (K+) levels, which mimics an action potential. The K+ spike brought mitochondria to a halt and prompted their division, making them shorter and rounder. These changes depended on the opening of voltage-dependent calcium channels and the resulting Ca2+ gradient, which in turn activates the Ca2+/calmodulin-dependent protein kinase (CaMKI{alpha}). A CaMKI{alpha} antagonist blocked K+-triggered changes in mitochondrial shape.

In their search for CaMKI{alpha} substrates, the authors turned to Drp1 (dynamin-related protein 1), which promotes mitochondrial fission and whose sequence suggested it could be phosphorylated. And the authors found that it was, in fact, a CaMKI{alpha} substrate. K+ treatment not only led to Drp1 phosphorylation, but caused cytoplasmic Drp1 to rapidly relocate to mitochondria and associate with another fission protein, Fis1. Together, these results indicate that a calcium influx is an important trigger for mitochondrial fission, and that Drp1 is a final effector of the fission signal.

Lead investigator Masayuki Matsushita says there is much more to discover about how calcium controls mitochondrial dynamics, including other roles for CaMKI{alpha}: "We think it may have other substrates as well, also involved in mitochondrial morphology."

Han, X.-J., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200802164.[Abstract/Free Full Text]



Richard Robinson

rrobinson{at}nasw.org


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