Mitochondrial calcium transport is regulated by P2Y1- and P2Y2-like mitochondrial receptors.

Belous AE, Jones CM, Wakata A, Knox CD, Nicoud IB, Pierce J, Chari RS
J Cell Biochem. 2006 99 (4): 1165-74

PMID: 16795051 · DOI:10.1002/jcb.20985

Ischemia-reperfusion injury remains a major clinical problem in liver transplantation. One contributing factor is mitochondrial calcium (mCa(2+)) overload, which triggers apoptosis; calcium also regulates mitochondrial respiration and adenosine 5'-triphosphate (ATP) production. Recently, we reported the presence of purinergic P2Y(1)- and P2Y(2)-like receptor proteins in mitochondrial membranes. Herein, we present an evaluation of the functional characteristics of these receptors. In experiments with isolated mitochondria, specific P2Y(1) and P2Y(2) receptors ligands: 2-methylthio-adenosine 5'-diphosphate (2meSADP) and uridine 5'-triphosphate (UTP), respectively, were used, and mitochondrial calcium uptake was measured. 2meSADP and UTP had a maximum effect at concentrations in the range of the known P2Y(1) and P2Y(2) receptors. The P2Y inhibitor phosphate-6-azophenyl-2',4'-disulfonate (PPADS) blocked the effects of both ligands. The phospholipase C (PLC) antagonist U73122 inhibited the effect of both ligands while its inactive analog U73343 had no effect. These data strongly support the hypothesis that mitochondrial Ca(2+) uptake is regulated in part by adenine nucleotides via a P2Y-like receptor mechanism that involves mitochondrial PLC activation.

MeSH Terms (18)

Adenosine Diphosphate Adenylyl Imidodiphosphate Animals Calcium Calcium Signaling Ion Transport Ligands Male Mitochondria Mitochondrial Proteins Models, Biological Purinergic P2 Receptor Agonists Rats Rats, Sprague-Dawley Receptors, Purinergic P2 Receptors, Purinergic P2Y1 Receptors, Purinergic P2Y2 Type C Phospholipases

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