Editors' ChoiceCell Biology

Intrinsic Signal to Stop

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Science Signaling  20 Sep 2011:
Vol. 4, Issue 191, pp. ec260
DOI: 10.1126/scisignal.4191ec260

Mitochondria are the cell’s energy power supply and are dynamic organelles that respond to cellular needs for energy and undergo changes in morphology and intracellular migration. Increases in intracellular calcium reduce mitochondrial motility, and increases in mitochondrial calcium promote ATP production. In cultured hippocampal neurons, Chang et al. applied real-time imaging of changes in mitochondrial calcium concentration and mitochondrial motility tracking and found that there was an inverse correlation between the intramitochondrial calcium concentration and motility, such that the lower the concentration of mitochondrial calcium, the faster the movement. Using pharmacological agents to manipulate the activity of the mitochondrial calcium uniporter, the authors found that mitochondria maintained their mobility in response to an increase in cytoplasmic calcium longer when the uniporter was blocked and that activation of the uniporter in the absence of an increase in cytoplasmic calcium caused the mitochondria to stop moving. (These changes in mobility were associated with the expected changes in mitochondrial calcium—high calcium when the uniporter was activated and low calcium when the uniporter was inhibited.) Miro1 is a mitochondria-associated protein with a calcium-binding EF hand that has been implicated in controlling mitochondrial movement. The increase in mitochondrial calcium in response to a calcium ionophore was reduced and mitochondrial movement persisted in cells expressing an EF hand mutant form of Miro1. Forced activation of the mitochondrial calcium uniporter bypassed the effect of the Miro1 EF hand mutant, suggesting that Miro1 acts upstream of the uniporter. Thus, an increase in mitochondrial calcium not only promotes ATP production but also halts the mitochondria so that they stay where the cellular energy demands are likely highest, at the site of an increase in cytosolic calcium.

K. T. Chang, R. F. Niescier, K.-T. Min, Mitochondrial matrix Ca2+ as an intrinsic signal regulating mitochondrial motility in axons. Proc. Natl. Acad. Sci. U.S.A. 108, 15456–15461 (2011). [Abstract] [Full Text]

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