Queliconi 2016 PLOS ONE
| Queliconi BB, Kowaltowski AJ, Gottlieb RA (2016) Bicarbonate increases ischemia-reperfusion damage by inhibiting mitophagy. PLOS ONE 11:e0167678. |
Queliconi BB, Kowaltowski AJ, Gottlieb RA (2016) PLOS ONE
Abstract: During an ischemic event, bicarbonate and CO2 concentration increase as a consequence of O2 consumption and lack of blood flow. This event is important as bicarbonate/CO2 is determinant for several redox and enzymatic reactions, in addition to pH regulation. Until now, most work done on the role of bicarbonate in ischemia-reperfusion injury focused on pH changes; although reperfusion solutions have a fixed pH, cardiac resuscitation protocols commonly employ bicarbonate to correct the profound acidosis associated with respiratory arrest. However, we previously showed that bicarbonate can increase tissue damage and protein oxidative damage independent of pH. Here we show the molecular basis of bicarbonate-induced reperfusion damage: the presence of bicarbonate selectively impairs mitophagy, with no detectable effect on autophagy, proteasome activity, reactive oxygen species production or protein oxidation. We also show that inhibition of autophagy reproduces the effects of bicarbonate in reperfusion injury, providing additional evidence in support of this mechanism. This phenomenon is especially important because bicarbonate is widely used in resuscitation protocols after cardiac arrest, and while effective as a buffer, may also contribute to myocardial injury.
• O2k-Network Lab: BR Sao Paulo Kowaltowski AJ
Labels: MiParea: Respiration
Stress:Ischemia-reperfusion Organism: Rat Tissue;cell: Heart Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET
Pathway: S, ROX
HRR: Oxygraph-2k
