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Mitochondrial channelopathies in aging

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Abstract

Defects in ion channels (channelopathies) are increasingly found in a large spectrum of human pathologies including aging. Mutations in genes encoding ion channel proteins, which disrupt channel function, are the most commonly identified cause of channelopathies. Mutations in associated proteins, alterations in the expression of ion channels, or changes in the activity of non-mutated channel genes or associated proteins can also produce acquired channelopathies. Mitochondria, the powerhouse of the cells, are considered to be the most important cellular organelles to contribute to aging mainly because of their role in the production of reactive oxygen species in the initiation of apoptotic cell remodeling and in efficient ATP synthesis. During the past 50 years, multiple ion channels or transporters have been found in mitochondria, and the relationship between the activity of these channels and cellular aging, as well as the overall cellular biological function, has been intensively studied in a number of cell types and animal models. In this review, we discuss the better characterized mitochondrial ion channels whose dysfunction (mitochondrial channelopathies) may affect or accelerate the aging processes. These channels include the mitochondrial ATP-sensitive potassium channel (mitoKATP), Ca2+ transporters, voltage-dependent anion channel, and the mitochondrial permeability transition pore (mitoPTP).

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Abbreviations

ANT:

adenine nucleotide translocator

ATP:

adenine triphosphate

ETC:

electron transport chain

FAO:

fatty acid oxidation

mitoKATP :

mitochondrial ATP-sensitive potassium channel

OXPHOS:

oxidative phosphorylation

PTP:

permeability transition pore

ROS:

reactive oxygen species

VDAC:

voltage-dependent anion channel

VGCCs:

voltage-gated Ca2+ channels

TCA:

tricarboxylate cycle

CP:

cardioprotection

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  1. The Molecular Cardiology and Neuromuscular Institute, 75 Raritan Avenue, Highland Park, NJ, 08904, USA

    YeQing Pi, Michael J. Goldenthal & José Marín-García

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  1. YeQing Pi
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Pi, Y., Goldenthal, M.J. & Marín-García, J. Mitochondrial channelopathies in aging. J Mol Med 85, 937–951 (2007). https://doi.org/10.1007/s00109-007-0190-5

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