Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery
Generating mammalian cells with specific mitochondrial DNA (mtDNA)–nuclear DNA (nDNA) combinations is desirable but difficult to achieve and would be enabling for studies of mitochondrial-nuclear communication and coordination in controlling cell fates and functions. We developed ‘MitoPunch’, a pres...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/63102 |
| _version_ | 1811202946641166336 |
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| author | Alexander J Sercel Alexander N Patananan Tianxing Man Ting-Hsiang Wu Amy K Yu Garret W Guyot Shahrooz Rabizadeh Kayvan R Niazi Pei-Yu Chiou Michael A Teitell |
| author_facet | Alexander J Sercel Alexander N Patananan Tianxing Man Ting-Hsiang Wu Amy K Yu Garret W Guyot Shahrooz Rabizadeh Kayvan R Niazi Pei-Yu Chiou Michael A Teitell |
| author_sort | Alexander J Sercel |
| collection | DOAJ |
| description | Generating mammalian cells with specific mitochondrial DNA (mtDNA)–nuclear DNA (nDNA) combinations is desirable but difficult to achieve and would be enabling for studies of mitochondrial-nuclear communication and coordination in controlling cell fates and functions. We developed ‘MitoPunch’, a pressure-driven mitochondrial transfer device, to deliver isolated mitochondria into numerous target mammalian cells simultaneously. MitoPunch and MitoCeption, a previously described force-based mitochondrial transfer approach, both yield stable isolated mitochondrial recipient (SIMR) cells that permanently retain exogenous mtDNA, whereas coincubation of mitochondria with cells does not yield SIMR cells. Although a typical MitoPunch or MitoCeption delivery results in dozens of immortalized SIMR clones with restored oxidative phosphorylation, only MitoPunch can produce replication-limited, non-immortal human SIMR clones. The MitoPunch device is versatile, inexpensive to assemble, and easy to use for engineering mtDNA–nDNA combinations to enable fundamental studies and potential translational applications. |
| first_indexed | 2024-04-12T02:46:15Z |
| format | Article |
| id | doaj.art-6c21484b522f4026ba665933a074bed6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:46:15Z |
| publishDate | 2021-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-6c21484b522f4026ba665933a074bed62022-12-22T03:51:09ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.63102Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial deliveryAlexander J Sercel0https://orcid.org/0000-0002-0749-2162Alexander N Patananan1https://orcid.org/0000-0001-9458-9968Tianxing Man2Ting-Hsiang Wu3Amy K Yu4Garret W Guyot5Shahrooz Rabizadeh6Kayvan R Niazi7Pei-Yu Chiou8Michael A Teitell9https://orcid.org/0000-0002-4495-8750Molecular Biology Interdepartmental Doctoral Program, University of California, Los Angeles, Los Angeles, United StatesDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, United StatesNanoCav, LLC, Culver City, United States; NantBio, Inc, and ImmunityBio, Inc, Culver City, United StatesMolecular Biology Interdepartmental Doctoral Program, University of California, Los Angeles, Los Angeles, United StatesDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesNanoCav, LLC, Culver City, United States; NantBio, Inc, and ImmunityBio, Inc, Culver City, United States; NantOmics, LLC, Culver City, United States; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United StatesNanoCav, LLC, Culver City, United States; NantBio, Inc, and ImmunityBio, Inc, Culver City, United States; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States; Department of Bioengineering, University of California, Los Angeles, Los Angeles, United StatesDepartment of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, United States; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States; Department of Bioengineering, University of California, Los Angeles, Los Angeles, United StatesMolecular Biology Interdepartmental Doctoral Program, University of California, Los Angeles, Los Angeles, United States; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States; Department of Bioengineering, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California, Los Angeles, Los Angeles, United States; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesGenerating mammalian cells with specific mitochondrial DNA (mtDNA)–nuclear DNA (nDNA) combinations is desirable but difficult to achieve and would be enabling for studies of mitochondrial-nuclear communication and coordination in controlling cell fates and functions. We developed ‘MitoPunch’, a pressure-driven mitochondrial transfer device, to deliver isolated mitochondria into numerous target mammalian cells simultaneously. MitoPunch and MitoCeption, a previously described force-based mitochondrial transfer approach, both yield stable isolated mitochondrial recipient (SIMR) cells that permanently retain exogenous mtDNA, whereas coincubation of mitochondria with cells does not yield SIMR cells. Although a typical MitoPunch or MitoCeption delivery results in dozens of immortalized SIMR clones with restored oxidative phosphorylation, only MitoPunch can produce replication-limited, non-immortal human SIMR clones. The MitoPunch device is versatile, inexpensive to assemble, and easy to use for engineering mtDNA–nDNA combinations to enable fundamental studies and potential translational applications.https://elifesciences.org/articles/63102mitochondrial dnamitochondrial transplantationMitoCeptionMitoPunchmitochondrial transferstable isolated mitochondrial recipient |
| spellingShingle | Alexander J Sercel Alexander N Patananan Tianxing Man Ting-Hsiang Wu Amy K Yu Garret W Guyot Shahrooz Rabizadeh Kayvan R Niazi Pei-Yu Chiou Michael A Teitell Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery eLife mitochondrial dna mitochondrial transplantation MitoCeption MitoPunch mitochondrial transfer stable isolated mitochondrial recipient |
| title | Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery |
| title_full | Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery |
| title_fullStr | Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery |
| title_full_unstemmed | Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery |
| title_short | Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery |
| title_sort | stable transplantation of human mitochondrial dna by high throughput pressurized isolated mitochondrial delivery |
| topic | mitochondrial dna mitochondrial transplantation MitoCeption MitoPunch mitochondrial transfer stable isolated mitochondrial recipient |
| url | https://elifesciences.org/articles/63102 |
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