Mitochondrial permeability transition pore-dependent necrosis. (January 2023)

• Record Type: Journal Article
• Authors: Robichaux, Dexter J.; Harata, Mikako; Murphy, Elizabeth; Karch, Jason
• Is Part Of: Journal of molecular and cellular cardiology. Volume 174(2023)
• Page Start: 47
• Page End: 55
• Publication Date: 2023-01
• Subjects: MPTP -- Necrosis -- Ischemia reperfusion -- Mitochondria -- Mitochondrial dysfunction -- ANT -- BAX -- BAK -- CypD -- ATP synthase -- Calcium -- ROS -- Permeability transition; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2022.11.003
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Mitochondrial permeability transition pore (mPTP)-dependent cell death is a form of necrotic cell death that is driven by mitochondrial dysfunction by the opening of the mPTP and is triggered by increases in matrix levels of Ca 2+ and reactive oxygen species. This form of cell death has been implicated in ischemic injuries of the heart and brain as well as numerous degenerative diseases in the brain and skeletal muscle. This review focuses on the molecular triggers and regulators of mPTP-dependent necrosis in the context of myocardial ischemia reperfusion injury. Research over the past 50 years has led to the identity of regulators and putative pore-forming components of the mPTP. Finally, downstream consequences of activation of the mPTP as well as ongoing questions and areas of research are discussed. These questions pose a particular interest as targeting the mPTP could potentially represent an efficacious therapeutic strategy to reduce infarct size following an ischemic event. Highlights: Ischemia reperfusion injury is a consequence of mPTP-dependent necrosis Prolonged mPTP opening leads to mitochondrial dysfunction mPTP opening is triggered by calcium and reactive oxygen species The mPTP may consist of multiple pore-forming entities Outer mitochondrial membrane permeability through the Bcl-2 family alters mPTP sensitivity to calcium