2016 SACNAS Graduate Student Oral Presentation Award

John Santiago, PhD candidate
Brown University
Providence, RI


Sexual asymmetry for mitochondrial function in response to TOR inhibition with rapamycin and RNAi in Drosophila
John Santiago and David Rand, Brown University, Providence, RI

Rapamycin has been shown to extend lifespan by potently inhibiting TOR (Target of Rapamycin) signaling, a major component of cellular metabolism. One fundamental yet poorly understood role of TOR is to modulate mitochondrial function. Previously we have shown that rapamycin enhances mitochondrial respiration in female flies, a beneficial effect that is eliminated in flies carrying a foreign mtDNA on the same D. melanogaster chromosomal background (Villa-Cuesta et al. 2014). Here we show a gender specific role of TOR signaling where rapamycin treatment increases mitochondrial oxygen consumption in female Drosophila but not in males. Interestingly, in D. melanogaster males carrying foreign mtDNA rapamycin increases mitochondrial respiration, unlike the effect in females. To better understand this sexually dimorphic response we utilized gene-switch induced RNAi knockdowns of the TOR-complex (TORC1) components Raptor and TOR. We test the hypothesis that genetic disruption of TORC1 will induce an effect similar to that seen in response to rapamycin treatment. Disruption of TORC1 in both females and males with either TOR or Raptor RNAi increased mitochondrial respiration. These results support a novel model in which this sexually dimorphic rapamycin response is not due to the absence of TORC1 signaling but to a sex specific function of rapamycin. Ongoing studies will examine the effects of alternative mtDNAs paired with RNAi against TOR, Raptor and Rictor to dissect the roles TORC1 and TORC2 in mitochondrial function. This model system provides novel approach to dissecting the gender-specific components of TOR signaling.

Long Beach, CA, October 13-15, 2016

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Dana Crawford

Professor of Population and Quantitative Health Sciences and Associate Director of the Cleveland Institute for Computational Biology, with interest in pharmacogenomics, electronic health records, and diverse populations. Also, an avid foodie!

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