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Recent progress in the use of mitochondrial membrane permeability transition pore in mitochondrial dysfunction-related disease therapies

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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 dysfunction-correlated 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.

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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

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, 3-Dimethoxy-5-methyl-1, 4-benzoquinone, zero isoprenoid side-chains

PAO:

Phenylarsine oxide

IBMX:

1-Methyl-3-isobutylxanthine

MIRI:

Mitochondrial ischemia/reperfusion injury

ETC:

Electron transport chain

Cas-3:

Caspase-3

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Funding

This publication was supported by National Natural Science Foundation of China (Grant No. 81900045) and Sanming Project of Medicine in Shenzhen (SZSM201801060).

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  1. Yuting Cui and Mingyue Pan have contributed equally.

Authors and Affiliations

  1. School of Life Science, Shandong University of Technology, Zibo, Shandong Province, China

    Yuting Cui & Xinhua Song

  2. Department of Pharmacy, Shenzhen Luohu People’s Hospital, Shenzhen, Guangdong Province, China

    Mingyue Pan, Weiling Cao & Peng Zhang

  3. The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong Province, China

    Jing Ma

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PZ contributed to suggesting ideas and critically revise the manuscript; YC and MP participated in original writing of the manuscript; JM and XS involved in literature search ; and WC did the data analysis .

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Cui, Y., Pan, M., Ma, J. et al. Recent progress in the use of mitochondrial membrane permeability transition pore in mitochondrial dysfunction-related disease therapies. Mol Cell Biochem 476, 493–506 (2021). https://doi.org/10.1007/s11010-020-03926-0

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