The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 13 No. 2 • April 2010

Kidney Injury and Recovery

Serotonin Receptor Stimulation
Increases Mitochondrial Biogenesis

In a new paper,1 researchers report that after acute injury, renal proximal tubular cells (RPTC) recover mitochondrial function by increasing the expression of the master regulator of mitochondrial biogenesis, PGC-1alpha (peroxisome-proliferator-activated-receptor-gamma-coactivator-1alpha). In this study, the authors examined the effects of 5-HT (serotonin) activators (agonists) on mitochondrial biogenesis in RPTC kidney cells, hypothesizing that 5-HT agonists may produce mitochondrial biogenesis in a variety of organs, including kidneys.

DOI, a selective agonist of 5-HT2 was found to increase the activity of PGC-1alpha in RPTC, which express the 2A, 2B, and 2C subtypes of the 5-HT receptor. They report that DOI-induced increases in mitochondrial biogenesis accelerated the recovery in RPTC of mitochondrial function after oxidative injury. They also report that another 5-HT2 receptor agonist m-chlorophenylpiperazine also increased mitochondrial biogenesis. They note that, “[a]lthough DOI is selective for 5-HT2 receptors, EC50 value for DOI [value that activates 50% of receptors] in isolated receptor systems is in the nanomolar range. This observation provides evidence that DOI may act as a more promiscuous activator of 5-HT receptor subtypes in this system and that the observed increases in mitochondrial biogenesis may be through other 5-HT receptors.”

The authors conclude that “... we suggest that DOI or other 5-HT receptor agonists may be an effective therapeutic option to accelerate the recovery of renal function subsequent to acute kidney injury.” Tryptophan (or 5-hydroxytryptophan) is an example of a nutrient that enhances activity of 5-HT (serotonin) receptors, in this case acting as the precursor to serotonin synthesis. The researchers also suggest that 5-HT reuptake inhibitors (SSRIs such as fluoxetine) may act through mitochondrial biogenesis.


  1. Rasbach et al. 5-hydroxytryptamine receptor stimulation of mitochondrial biogenesis. J Pharmacol Exp Ther 332(2):632-9 (2010).

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