Mitochondrial PKA mediates sperm motility

Rashel Mizrahi, Haim Breitbart

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background Mitochondria are the major source of ATP to power sperm motility. Phosphorylation of mitochondrial proteins has been proposed as a major regulatory mechanism for mitochondrial bioenergetics. Methods Sperm motility was measured by a computer-assisted analyzer, protein detection by western blotting, membrane potential by tetramethylrhodamine, cellular ATP by luciferase assay and localization of PKA by immuno-electron microscopy. Results Bicarbonate is essential for the creation of mitochondrial electro-chemical gradient, ATP synthesis and sperm motility. Bicarbonate stimulates PKA-dependent phosphorylation of two 60 kDa proteins identified as Tektin and glucose-6-phosphate isomerase. This phosphorylation was inhibited by respiration inhibition and phosphorylation could be restored by glucose in the presence of bicarbonate. However, this effect of glucose cannot be seen when the mitochondrial ATP/ADP exchanger was inhibited indicating that glycolytic-produced ATP is transported into the mitochondria and allows PKA-dependent protein phosphorylation inside the mitochondria. Conclusions Bicarbonate activates mitochondrial soluble adenylyl cyclase (sAC) which catalyzes cAMP production leading to the activation of mitochondrial PKA. Glucose can overcome the lack of ATP in the absence of bicarbonate but it cannot affect the mitochondrial sAC/PKA system, therefore the PKA-dependent phosphorylation of the 60 kDa proteins does not occur in the absence of bicarbonate. General significance Production of CO2 in Krebs cycle, which is converted to bicarbonate is essential for sAC/PKA activation leading to mitochondrial membrane potential creation and ATP synthesis.

Original languageEnglish
Pages (from-to)3404-3412
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Issue number12
StatePublished - Dec 2014

Bibliographical note

Publisher Copyright:
© 2014 Elsevier B.V.


  • Mitochondria
  • Motility
  • PKA
  • Soluble adenylyl cyclase
  • Spermatozoa


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