Recent progress in the use of mitochondrial membrane permeability transition pore in mitochondrial dysfunction-related d
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Recent progress in the use of mitochondrial membrane permeability transition pore in mitochondrial dysfunction‑related disease therapies Yuting Cui1 · Mingyue Pan2 · Jing Ma3 · Xinhua Song1 · Weiling Cao2 · Peng Zhang2 Received: 8 May 2020 / Accepted: 23 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Mitochondria have various cellular functions, including ATP synthesis, calcium homeostasis, cell senescence, and death. Mitochondrial dysfunction has been identified in a variety of disorders correlated with human health. Among the many underlying mechanisms of mitochondrial dysfunction, the opening up of the mitochondrial permeability transition pore (mPTP) is one that has drawn increasing interest in recent years. It plays an important role in apoptosis and necrosis; however, the molecular structure and function of the mPTP have still not been fully elucidated. In recent years, the abnormal opening up of the mPTP has been implicated in the development and pathogenesis of diverse diseases including ischemia/reperfusion injury (IRI), neurodegenerative disorders, tumors, and chronic obstructive pulmonary disease (COPD). This review provides a systematic introduction to the possible molecular makeup of the mPTP and summarizes the mitochondrial dysfunctioncorrelated diseases and highlights possible underlying mechanisms. Since the mPTP is an important target in mitochondrial dysfunction, this review also summarizes potential treatments, which may be used to inhibit pore opening up via the molecules composing mPTP complexes, thus suppressing the progression of mitochondrial dysfunction-related diseases. Keywords Mitochondrial permeability transition pore (mPTP) · Translocator protein (TSPO) · Mitochondrial dysfunction · Tumor · Respiratory diseases Abbreviations mPTP Mitochondrial permeability transition pore IRI Ischemia/reperfusion injury COPD Chronic obstructive pulmonary disease OMM Outer mitochondrial membrane IMM Inner mitochondrial membrane MPT Mitochondrial permeability transition MMP Mitochondrial membrane potential Cyt c Cytochrome c VDAC Voltage-dependent anion channel Yuting Cui and Mingyue Pan have contributed equally. * Weiling Cao [email protected] * Peng Zhang [email protected] 1
School of Life Science, Shandong University of Technology, Zibo, Shandong Province, China
2
Department of Pharmacy, Shenzhen Luohu People’s Hospital, Shenzhen, Guangdong Province, China
3
The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong Province, China
ANT Adenine nucleotide translocator Cyp-D Cyclophilin D PiC Phosphate carrier TSPO Translocator protein CsA Cyclosporine A SPG7 Spastic paraplegia 7 Bcl-2 Apoptosis protein B cell leukemia/lymphoma-2 BI-1 Bax inhibitor-1 ER Endoplasmic reticulum CDZ 4′-Chlorodiazepam CNS Central nervous system AD Alzheimer’s disease PD Parkinson’s disease HD Huntington’s disease ALS Amyotrophic lateral sclerosis CSC Cancer stem cells CS Cigarette smoking BKA Bongkrekic acid CoQ0 2,
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