Mitochondrial P2Y-Like receptors link cytosolic adenosine nucleotides to mitochondrial calcium uptake

✍ Scribed by Andrey Belous; Aya Wakata; Clayton D. Knox; Ian B. Nicoud; Janene Pierce; Christopher D. Anderson; C. Wright Pinson; Ravi S. Chari

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 348 KB
• Volume: 92
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20144

✦ Synopsis

ATP is a known extracellular ligand for cell membrane purinergic receptors. Intracellular ATP can work also as a regulatory ligand via binding sites on functional proteins. We report herein the existence of P2Y 1 -like and P2Y 2like receptors in hepatocyte mitochondria (mP2Y 1 and mP2Y 2 ), which regulate mCa 2þ uptake though the uniporter. Mitochondrial P2Y 1 activation stimulates mCa 2þ uptake; whereas, mP2Y 2 activation inhibits mCa 2þ uptake. ATP acts preferentially on mP2Y 2 receptors, while ADP and AMP-PNP stimulate both the mP2Y 1 and mP2Y 2 . PPADS inhibits ADP stimulated mP2Y 1 -mediated mCa 2þ uptake. In addition, UTP, a selective P2Y 2 agonist, strongly inhibits mCa 2þ uptake. The newly discovered presence and function of these receptors is significant because it explains increased mCa 2þ uptake in the setting of low cytosolic [ATP] and, therefore, establishes a mechanism for direct feedback in which cytosolic [ATP] governs mitochondrial ATP production through regulation of mCa 2þ uptake.