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New mitochondria-specific photoactivation probe to monitor sphingolipid metabolism and function

The collaborative efforts between several departments of the University of Geneva, Switzerland, the EPF Lausanne and the NCCR Chemical Biology are recently reported in eLife. The work describes the use of a new mitochondria-specific photoactivation tool to monitor local  sphingosine metabolism and function. Their combined results provide direct evidence that sphingosine has distinct metabolism and signaling patterns depending on subcellular localization.

Photoactivation (“uncaging”) is a powerful approach for releasing bioactive small-molecules in living cells. Current uncaging methods are limited by the random distribution of caged molecules within cells. The authors have developed a mitochondria-specific photoactivation method, which permitted them to release free sphingosine inside mitochondria and thereafter monitor local sphingosine metabolism by lipidomics. Results indicate that sphingosine is quickly phosphorylated into sphingosine 1-phosphate (S1P) driven by sphingosine kinases. In time-course studies, the mitochondria-specific uncaged sphingosine demonstrated distinct metabolic patterns compared to globally-released sphingosine, and did not induce calcium spikes. The data provide direct evidence that sphingolipid metabolism and signaling are highly dependent on the subcellular location and opens up new possibilities to study the effects of lipid localization on signaling and metabolic fate.

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Suihan Feng, Takeshi Harayama, Sylvie Montessuit, Fabrice PA David, Nicolas Winssinger, Jean-Claude Martinou, Howard Riezman,  Mitochondria-specific photoactivation to monitor local sphingosine metabolism and function“, eLife 2018;7:e34555 DOI: 10.7554/eLife.34555

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