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Vitamin D action on mitochondria – July 2024

Genomic and non-genomic action of vitamin D on ion channels – Targeting mitochondria

Mitochondrion Volume 77, July 2024, https://doi.org/10.1016/j.mito.2024.101891
A.M. Olszewska, M.A. Zmijewski


  • Mitochondria are place of vitamin D metabolism and the target of its activities.
  • Vitamin D influences the activity of membrane and mitochondrial ion channels.
  • Genomic pathways regulated by vitamin D directly or indirectly regulate genes encoding mitochondrial ion channels.
  • Vitamin D might have direct impact on conductivity of mitochondrial channel proteins.

Recent studies revealed that mitochondria are not only a place of vitamin D3 metabolism but also direct or indirect targets of its activities. This review summarizes current knowledge on the regulation of ion channels from plasma and mitochondrial membranes by the active form of vitamin D3 (1,25(OH)2D3). 1,25(OH)2D3, is a naturally occurring hormone with pleiotropic activities; implicated in the modulation of cell differentiation, and proliferation and in the prevention of various diseases, including cancer. Many experimental data indicate that 1,25(OH)2D3 deficiency induces ionic remodeling and 1,25(OH)2D3 regulates the activity of multiple ion channels. There are two main theories on how 1,25(OH)2D3 can modify the function of ion channels. First, describes the involvement of genomic pathways of response to 1,25(OH)2D3 in the regulation of the expression of the genes encoding channels, their auxiliary subunits, or additional regulators. Interestingly, intracellular ion channels, like mitochondrial, are encoded by the same genes as plasma membrane channels. Therefore, the comprehensive genomic regulation of the channels from these two different cellular compartments we analyzed using a bioinformatic approach. The second theory explores non-genomic pathways of vitamin D3 activities. It was shown, that 1,25(OH)2D3 indirectly regulates enzymes that impact ion channels, change membrane physical properties, or directly bind to channel proteins. In this article, the involvement of genomic and non-genomic pathways regulated by 1,25(OH)2D3 in the modulation of the levels and activity of plasma membrane and mitochondrial ion channels was investigated by an extensive review of the literature and analysis of the transcriptomic data using bioinformatics.
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Abbreviations: Perhaps the longest list in VitaminDWiki
1,25(OH)2D3 calcitriolthe active form of vitamin D31,25D3-MARRSmembrane-associated rapid response to steroid25(OH)2D3calcidiol7DHC7-dehydrocholesterolA431squamous carcinoma cell lineADAM10A disintegrin and metalloproteinase domain 10ANO1anoctamin 1APPamyloid precursor proteinBODIPYboron-dipyrrometheneC2C12mouse myoblast cell lineCAV1caveolin-1Cav1.3L-type Ca2+ channelsCAV3caveolin-3CLCN2chloride voltage-gated channel 2CLICchloride intracellular channelsCLIC4chloride intracellular channel type 4CLIC5chloride intracellular channel type 5CO-IPco-immunoprecipitationCOXIIcytochrome c oxidase subunit IICPT1bcarnitine palmitoyltransferase 1CRAC1cholesterol binding motifCYP1B1cytochrome P450 family 1 subfamily B member 1CYP24A1cytochrome P450 family 24 subfamily A member 1CYP27A1cytochrome P450 family 27 subfamilies A member 1CYP27B1cytochrome P450 Family 27 Subfamily B Member 1Cyp2R1cytochrome P450 family 2 subfamily R member 1DEGsdifferentially expressed genesD-loopdisplacement loopDRP1dynamin-related protein 1EAG1ether à-go-go-1 channelElovl3elongation of very long chain fatty acids-3ERp57endoplasmic reticulum resident protein 57ETCelectron transport chainFIS1mitochondrial fission 1 proteinGHShypercalciuric stone-formingHDAChistone deacetylaseHEKnhuman epidermal keratinocytes neonatalHK-2a proximal tubular cell line derived from normal kidneyHPEKpprimary human epidermal keratinocytesK+-ATPATP-regulated potassium channelsK+-Ca2+calcium regulated potassium channelsKCNE4potassium voltage-gated channel subfamily E regulatory subunit 4KCNH1potassium voltage-gated channel subfamily H member 1KCNJ11potassium inwardly rectifying channel subfamily J member 11KCNK9two-pore domain potassium channels type 9KCNMA1potassium calcium-activated channel subfamily M alpha 1KCNMA1 STREXpotassium calcium-activated channel subfamily M alpha 1 with stress-axis regulated exonKCNMB4potassium calcium-activated channel subfamily M regulatory beta subunit 4KCNNintermediate/small conductance calcium-activated channel, subfamily NKCNN1potassium calcium-activated channel subfamily N member 1KCNN2potassium calcium-activated channel subfamily N member 2KCNN3potassium calcium-activated channel subfamily N member 3KCNN4potassium calcium-activated channel subfamily N member 4KCNQ1potassium voltage-gated channel subfamily Q member 1KCTD14potassium channel tetramerization domain containing 14Kvvoltage-regulated potassium channelsKv7potassium *voltage-gated channel subfamily Q member 1LRP2/CUBNmegalin/cubilinL-type VDCCL-type voltage-gated channelsMCF-7breast cancer cell lineMCUmitochondrial calcium uniporterMFN1/2mitofusin-1/2MG-63human osteosarcoma cell linemitoBKCamitochondrial large conductance calcium-regulated potassium channelmitoBKCaDEC mitochondrial large conductance potassium channel DEC isoformmitoDEGsmitochondrial differentially expressed genesmitoHCNmitochondrial hyperpolarization-activated cyclic nucleotide-gated channelmitoIKCamitochondrial intermediate conductance calcium-regulated potassium channelmitoKATPmitochondrial ATP-sensitive potassium channelmitoKv1.3mitochondrial 1.3 voltage-gated potassium channelmitoKv1.5mitochondrial 1.5 voltage-gated potassium channelmitoKv7.4mitochondrial 7.4 voltage-gated potassium channelmitoSKCamitochondrial small conductance calcium-regulated potassium channelmitoSLO2mitochondrial sodium-activated potassium channelmitoTASK-3mitochondrial two-pore domain potassium channelMT-ATP6mitochondrially Encoded ATP Synthase Membrane Subunit 6MT-ATP8mitochondrially Encoded ATP Synthase Membrane Subunit 8MTCO1mitochondrially Encoded Cytochrome C Oxidase ImtDNAmitochondrial DNAMT-ND3mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 3MT-ND4mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4MT-ND5mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 5OPA1optic atrophy 1OXPHOSoxidative phosphorylationPASMCpulmonary artery smooth muscle cellsPCphosphatidylcholinePDIA3protein disulfide isomerase family A member 3PGC-1αperoxisome proliferator-activated receptor gamma coactivator-1alphaPKAprotein kinase APLA2phospholipase A2PTPpermeability transition poreRXRAretinoid X receptor alphaSERCAsarcoplasmic/endoplasmic reticulum Ca2+-ATPaseSHHsonic hedgehog signalingSH-SY5Yneuroblastoma cell line from a metastatic bone tumorSTREXstress-axis regulated exonTASKTWIK-related acid-sensitive K+ channel, two-pore domainTFAMmitochondrial transcription factor ATGFβtransforming growth factor-βTHP-1human monocytic cellsTMEM16Atransmembrane Protein 16ATOM/TIMmitochondrial translocaseTRPVtransient receptor potential cation channel subfamily VTRPV5transient receptor potential cation channel subfamily V type 5TRPV6transient receptor potential cation channel subfamily V type 6UCP3uncoupling Protein 3UVBultraviolet BVDACvoltage-dependent anion channelVDRvitamin D receptorVDREvitamin D receptor response elements

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Vitamin D action on mitochondria – July 2024        
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