Details

Autor(en) / Beteiligte

• Wiczer, Brian M.
• Marcu, Raluca
• Hawkins, Brian J.

Titel

KB-R7943, a plasma membrane Na+/Ca2+ exchanger inhibitor, blocks opening of the mitochondrial permeability transition pore

Ist Teil von

• Biochemical and biophysical research communications, 2014-01, Vol.444 (1), p.44-49

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2014

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •KB-R7943 did not block mitochondrial calcium uptake.•KB-R7943 increased the mitochondrial calcium retention capacity.•KB-R7943 protected against Ca2+ ionophore-induced mPTP opening and cell death. The isothiourea derivative, KB-R7943, inhibits the reverse-mode of the plasma membrane sodium/calcium exchanger and protects against ischemia/reperfusion injury. The mechanism through which KB-R7943 confers protection, however, remains controversial. Recently, KB-R7943 has been shown to inhibit mitochondrial calcium uptake and matrix overload, which may contribute to its protective effects. While using KB-R7943 for this purpose, we find here no evidence that KB-R7943 directly blocks mitochondrial calcium uptake. Rather, we find that KB-R7943 inhibits opening of the mitochondrial permeability transition pore in permeabilized cells and isolated liver mitochondria. Furthermore, we find that this observation correlates with protection against calcium ionophore-induced mitochondrial membrane potential depolarization and cell death, without detrimental effects to basal mitochondrial membrane potential or complex I-dependent mitochondrial respiration. Our data reveal another mechanism through which KB-R7943 may protect against calcium-induced injury, as well as a novel means to inhibit the mitochondrial permeability transition pore.