Recent studies show that the activation of mTORC1 regulates glutamine metabolism by regulating glutamate dehydrogenase and repressing the transcription of SIRT4 (Csibi et. al 2013).
SIRT4 is a mitochondrial protein of the sirtuin family that ribosylates and inhibits gdh. It is proposed that SIRT4 may function as regulator between metabolism and age-related diseases such as cancer and metabolic syndromes (Zhu et al.2014).
Furthermore, SIRT4 promotes longevity in fruit flies and energy homeostasis In particular, SIRT4 regulates metabolic pathways such as glycolysis, TCA cycle, and oxidative phosphorylation in response to the environmental and nutrient conditions (Wood et al. 2018). Preliminary results obtained by an graduate student in our laboratory compared the oxygen consumption of SIRT4 mutants of D. melanogaster and wild-type flies under rapamycin and control treatment. In particular, the oxygen consumption of SIRT4 mutants of D.melanogaster in rapamycin treatment was decreased but significantly less than in wild-type flies under rapamycin treatment.
The SIRT4 mutants of D. melanogaster in rapamycin treatment had less effect on the oxygen consumption than the control treatment. The results suggested that SIRT4 is not necessary for rapamycin to decrease oxygen consumption, but at least some of the effect of rapamycin on metabolic rate seems to require SIRT4. Since SIRT4 regulates gdh, rapamycin might be involved in the inhibition of glutamine catabolism.