The functional organization of mitochondrial genomes in human cells
Background: We analyzed the organization and function of mitochondrial DNA in a stable human cell line (ECV304, which is also known as T-24) containing mitochondria tagged with the yellow fluorescent protein. Results: Mitochondrial DNA is organized in ~475 discrete foci containing 6–10 genomes. Thes...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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BioMed Central
2004
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| _version_ | 1826301755213742080 |
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| author | Iborra, F Kimura, H Cook, P |
| author_facet | Iborra, F Kimura, H Cook, P |
| author_sort | Iborra, F |
| collection | OXFORD |
| description | Background: We analyzed the organization and function of mitochondrial DNA in a stable human cell line (ECV304, which is also known as T-24) containing mitochondria tagged with the yellow fluorescent protein. Results: Mitochondrial DNA is organized in ~475 discrete foci containing 6–10 genomes. These foci (nucleoids) are tethered directly or indirectly through mitochondrial membranes to kinesin, marked by KIF5B, and microtubules in the surrounding cytoplasm. In living cells, foci have an apparent diffusion constant of 1.1 × 10-3 μm2/s, and mitochondria always split next to a focus to distribute all DNA to one daughter. The kinetics of replication and transcription (monitored by immunolabelling after incorporating bromodeoxyuridine or bromouridine) reveal that each genome replicates independently of others in a focus, and that newly-made RNA remains in a focus (residence half-time ~43 min) long after it has been made. This mitochondrial RNA colocalizes with components of the cytoplasmic machinery that makes and imports nuclear-encoded proteins – that is, a ribosomal protein (S6), a nascent peptide associated protein (NAC), and the translocase in the outer membrane (Tom22). Conclusions: The results suggest that clusters of mitochondrial genomes organize the translation machineries on both sides of the mitochondrial membranes. Then, proteins encoded by the nuclear genome and destined for the mitochondria will be made close to mitochondrial-encoded proteins so that they can be assembled efficiently into mitochondrial complexes. |
| first_indexed | 2024-03-07T05:37:09Z |
| format | Journal article |
| id | oxford-uuid:e44e1644-abfd-4f48-a619-c2edbef75195 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:37:09Z |
| publishDate | 2004 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:e44e1644-abfd-4f48-a619-c2edbef751952022-03-27T10:15:35ZThe functional organization of mitochondrial genomes in human cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e44e1644-abfd-4f48-a619-c2edbef75195PathologyGene medicineMedical SciencesGenetics (life sciences)EnglishOxford University Research Archive - ValetBioMed Central2004Iborra, FKimura, HCook, PBackground: We analyzed the organization and function of mitochondrial DNA in a stable human cell line (ECV304, which is also known as T-24) containing mitochondria tagged with the yellow fluorescent protein. Results: Mitochondrial DNA is organized in ~475 discrete foci containing 6–10 genomes. These foci (nucleoids) are tethered directly or indirectly through mitochondrial membranes to kinesin, marked by KIF5B, and microtubules in the surrounding cytoplasm. In living cells, foci have an apparent diffusion constant of 1.1 × 10-3 μm2/s, and mitochondria always split next to a focus to distribute all DNA to one daughter. The kinetics of replication and transcription (monitored by immunolabelling after incorporating bromodeoxyuridine or bromouridine) reveal that each genome replicates independently of others in a focus, and that newly-made RNA remains in a focus (residence half-time ~43 min) long after it has been made. This mitochondrial RNA colocalizes with components of the cytoplasmic machinery that makes and imports nuclear-encoded proteins – that is, a ribosomal protein (S6), a nascent peptide associated protein (NAC), and the translocase in the outer membrane (Tom22). Conclusions: The results suggest that clusters of mitochondrial genomes organize the translation machineries on both sides of the mitochondrial membranes. Then, proteins encoded by the nuclear genome and destined for the mitochondria will be made close to mitochondrial-encoded proteins so that they can be assembled efficiently into mitochondrial complexes. |
| spellingShingle | Pathology Gene medicine Medical Sciences Genetics (life sciences) Iborra, F Kimura, H Cook, P The functional organization of mitochondrial genomes in human cells |
| title | The functional organization of mitochondrial genomes in human cells |
| title_full | The functional organization of mitochondrial genomes in human cells |
| title_fullStr | The functional organization of mitochondrial genomes in human cells |
| title_full_unstemmed | The functional organization of mitochondrial genomes in human cells |
| title_short | The functional organization of mitochondrial genomes in human cells |
| title_sort | functional organization of mitochondrial genomes in human cells |
| topic | Pathology Gene medicine Medical Sciences Genetics (life sciences) |
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