Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity
Human mitochondrial DNA (mtDNA) is a 16.9 kbp double-stranded, circular DNA, encoding subunits of the oxidative phosphorylation electron transfer chain and essential RNAs for mitochondrial protein translation. The minimal human mtDNA replisome is composed of the DNA helicase Twinkle, DNA polymerase...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/4/1796 |
| _version_ | 1797619025884217344 |
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| author | Joon Park Noe Baruch-Torres Y. Whitney Yin |
| author_facet | Joon Park Noe Baruch-Torres Y. Whitney Yin |
| author_sort | Joon Park |
| collection | DOAJ |
| description | Human mitochondrial DNA (mtDNA) is a 16.9 kbp double-stranded, circular DNA, encoding subunits of the oxidative phosphorylation electron transfer chain and essential RNAs for mitochondrial protein translation. The minimal human mtDNA replisome is composed of the DNA helicase Twinkle, DNA polymerase γ, and mitochondrial single-stranded DNA-binding protein. While the mitochondrial RNA transcription is carried out by mitochondrial RNA polymerase, mitochondrial transcription factors TFAM and TFB2M, and a transcription elongation factor, TEFM, both RNA transcriptions, and DNA replication machineries are intertwined and control mtDNA copy numbers, cellular energy supplies, and cellular metabolism. In this review, we discuss the mechanisms governing these main pathways and the mtDNA diseases that arise from mutations in transcription and replication machineries from a structural point of view. We also address the adverse effect of antiviral drugs mediated by mitochondrial DNA and RNA polymerases as well as possible structural approaches to develop nucleoside reverse transcriptase inhibitor and ribonucleosides analogs with reduced toxicity. |
| first_indexed | 2024-03-11T08:21:06Z |
| format | Article |
| id | doaj.art-8094e99a01ed46d5b0f93c3474e838e0 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T08:21:06Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8094e99a01ed46d5b0f93c3474e838e02023-11-16T22:23:19ZengMDPI AGMolecules1420-30492023-02-01284179610.3390/molecules28041796Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug ToxicityJoon Park0Noe Baruch-Torres1Y. Whitney Yin2Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USAHuman mitochondrial DNA (mtDNA) is a 16.9 kbp double-stranded, circular DNA, encoding subunits of the oxidative phosphorylation electron transfer chain and essential RNAs for mitochondrial protein translation. The minimal human mtDNA replisome is composed of the DNA helicase Twinkle, DNA polymerase γ, and mitochondrial single-stranded DNA-binding protein. While the mitochondrial RNA transcription is carried out by mitochondrial RNA polymerase, mitochondrial transcription factors TFAM and TFB2M, and a transcription elongation factor, TEFM, both RNA transcriptions, and DNA replication machineries are intertwined and control mtDNA copy numbers, cellular energy supplies, and cellular metabolism. In this review, we discuss the mechanisms governing these main pathways and the mtDNA diseases that arise from mutations in transcription and replication machineries from a structural point of view. We also address the adverse effect of antiviral drugs mediated by mitochondrial DNA and RNA polymerases as well as possible structural approaches to develop nucleoside reverse transcriptase inhibitor and ribonucleosides analogs with reduced toxicity.https://www.mdpi.com/1420-3049/28/4/1796mitochondriaDNA replicationRNA transcriptionhuman diseasesantiviralsHIV |
| spellingShingle | Joon Park Noe Baruch-Torres Y. Whitney Yin Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity Molecules mitochondria DNA replication RNA transcription human diseases antivirals HIV |
| title | Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity |
| title_full | Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity |
| title_fullStr | Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity |
| title_full_unstemmed | Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity |
| title_short | Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity |
| title_sort | structural and molecular basis for mitochondrial dna replication and transcription in health and antiviral drug toxicity |
| topic | mitochondria DNA replication RNA transcription human diseases antivirals HIV |
| url | https://www.mdpi.com/1420-3049/28/4/1796 |
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