Elucidation of cGMP-dependent induction of mitochondrial biogenesis through PKG and p38 MAPK in the kidney

Pallavi Bhargava, Jaroslav Janda, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Previous studies have shown that cGMP increases mitochondrial biogenesis (MB). Our laboratory has determined that formoterol and LY344864, agonists of the β2-adrenergic receptor and 5-HT1F receptor, respectively, signal MB in a soluble guanylyl cyclase (sGC)-dependent manner. However, the pathway between cGMP and MB produced by these pharmacological agents in renal proximal tubule cells (RPTCs) and the kidney has not been determined. In the present study, we showed that treatment of RPTCs with formoterol, LY344864, or riociguat, a sGC stimulator, induces MB through protein kinase G (PKG), a target of cGMP, and p38, an associated downstream target of PKG and a regulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in RPTCs. We also examined if p38 plays a role in PGC-1α phosphorylation in vivo. Administration of L-skepinone, a potent and specific inhibitor of p38α and p38β, to naïve mice inhibited phosphorylated PGC-1α localization in the nuclear fraction of the renal cortex. Taken together, we demonstrated a pathway, sGC/cGMP/ PKG/p38/PGC-1α, for pharmacological induction of MB and the importance of p38 in this pathway.

Original languageEnglish (US)
Pages (from-to)F322-F328
JournalAmerican Journal of Physiology - Renal Physiology
Issue number2
StatePublished - Feb 2020


  • Biogenesis
  • CGMP
  • Guanylyl cyclase
  • Mitochondria
  • Mitogen-activated protein kinase
  • Protein kinase G
  • Renal repair

ASJC Scopus subject areas

  • Physiology
  • Urology


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