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Research Article

Accumulation of an Antidepressant in Vesiculogenic Membranes of Yeast Cells Triggers Autophagy

  • Jingqiu Chen equal contributor,

    equal contributor Contributed equally to this work with: Jingqiu Chen, Daniel Korostyshevsky

    Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America

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  • Daniel Korostyshevsky equal contributor,

    equal contributor Contributed equally to this work with: Jingqiu Chen, Daniel Korostyshevsky

    Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America

    X
  • Sean Lee,

    Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America

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  • Ethan O. Perlstein mail

    eperlste@princeton.edu

    Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America

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  • Published: April 18, 2012
  • DOI: 10.1371/journal.pone.0034024

Reader Comments (16)

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Question

Posted by LGiuffra on 01 Oct 2012 at 02:23 GMT

Nice website. A quick question: how specific to antidepressants (or psychotropics) are the effects of sertraline in yeast membrane? What other drugs that are not psychotropics do the same, and what other antidepressants don't? I'm having a hard time leaping from your interesting finding to suggesting it may have something to do with antidepressant effects....

No competing interests declared.

RE: Question

eperlste replied to LGiuffra on 05 Oct 2012 at 20:02 GMT

Great question. We haven't tested the entire FDA pharmacopeia but we've looked at a lot of psychoactive drugs, and a dozen or so non-psychoactives. Short answer is membrane accumulation is a general property of cationic amphipaths, but there appears to be specificity of accumulation.

For example, we've done EM studies on yeast cells treated with amiodarone, an antiarrhythmic agent. We see evidence of membrane accumulation, but the ultrastructural features are not identical to those of sertraline-treated yeast cells, though there is overlap.

In work that is being written up now, we've looked for specificity determinants of membrane accumulation by a diverse set of psychoactive drugs, including multiple generations of antidepressants, antipsychotics and antihistamines. Yeast cells can actually tell the difference between closely related drugs, e.g., secondary amine tricyclics vs tertiary amine tricyclics. I think there's this notion that drug-membrane interactions are necessarily non-specific, but I don't believe this to be the case.

As for connecting membrane accumulation back to antidepressant effects on the brain, we proposed a simple model in the discussion of this paper. We are in the process of finding collaborators who would be interested in testing our ideas. If you know any good mouse psychiatrists, please forward my contact info! ;)

No competing interests declared.