Inhibition of Bcl-2 sensitizes mitochondrial permeability transition pore (MPTP) opening in ischemia-damaged mitochondria

PloS One
Qun ChenEdward J Lesnefsky

Abstract

Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes. Calcium retention capacity (CRC) was used to reflect the sensitivity of the MPTP opening in isolated cardiac mitochondria. To study the relationship between bcl-2 inhibition and MPTP opening, mitochondria were incubated with a bcl-2 inhibitor (HA14-1) and CRC measured. The contribution of preserved bcl-2 content to MPTP opening following ischemia-reperfusion was explored using transgenic bcl-2 overexpressed mice. CRC was decreased in mitochondria following reperfusion compared to ischemia alone, indicating that reperfusion further sensitizes to MPTP opening. Incubation of ischemia-damaged mitochondria with in...Continue Reading

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Citations

Jan 17, 2016·Biochimica Et Biophysica Acta·Mart BittremieuxGeert Bultynck
Jan 18, 2016·Biochimica Et Biophysica Acta·Geoffrey W ChoJoseph A Hill
Jan 21, 2016·Oxidative Medicine and Cellular Longevity·Daoxu QuDong Wang
Aug 12, 2015·Biochimica Et Biophysica Acta·Qun Chen, Edward J Lesnefsky
Oct 6, 2015·Advances in Pharmacological Sciences·Syed Suhail AndrabiHeena Tabassum
Apr 22, 2017·Clinical and Experimental Pharmacology & Physiology·Yue ZhangXiuping Han
May 7, 2020·International Journal of Molecular Sciences·Krestinina OlgaPapadopoulos Vassilios
Jun 27, 2019·Journal of Neurophysiology·Fahad IqbalNaweed I Syed
Mar 2, 2021·Molecular and Cellular Biochemistry·Ritesh Kumar SrivastavArshiya Shamim
Oct 21, 2021·The FEBS Journal·Robert E Means, Samuel G Katz

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