Mitochondrial PKA mediates sperm motility

Rashel Mizrahi1, Haim Breitbart1

  • 1The Mina & Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.

Abstract

Insights

Bicarbonate is crucial for sperm motility by activating mitochondrial soluble adenylyl cyclase (sAC) and protein kinase A (PKA), which are essential for ATP production. Glucose can restore ATP levels but cannot replace bicarbonate

Area of Science:

  • Sperm physiology
  • Mitochondrial bioenergetics
  • Cellular metabolism

Background:

  • Mitochondria generate ATP, powering sperm motility.
  • Protein phosphorylation is a key regulator of mitochondrial function.

Purpose of the Study:

  • To investigate the role of bicarbonate in sperm mitochondrial bioenergetics and motility.
  • To elucidate the signaling pathway involving soluble adenylyl cyclase (sAC) and protein kinase A (PKA) in sperm.

Main Methods:

  • Computer-assisted sperm motility analysis.
  • Western blotting for protein detection.
  • Tetramethylrhodamine for membrane potential assessment.
  • Luciferase assay for cellular ATP quantification.
  • Immuno-electron microscopy for PKA localization.

Main Results:

  • Bicarbonate is essential for mitochondrial membrane potential, ATP synthesis, and sperm motility.
  • Bicarbonate stimulates PKA-dependent phosphorylation of Tektin and glucose-6-phosphate isomerase (60kDa proteins).
  • Glycolytic ATP can be transported into mitochondria to support PKA-dependent phosphorylation in the presence of bicarbonate.

Conclusions:

  • Bicarbonate activates mitochondrial sAC, leading to cAMP production and PKA activation.
  • sAC/PKA activation is critical for mitochondrial membrane potential and ATP synthesis.
  • While glucose can supplement ATP, it cannot substitute for bicarbonate in activating the sAC/PKA pathway for essential protein phosphorylation.

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