Eintrag weiter verarbeiten
Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms
Gespeichert in:
| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 117, 2020, 50, S. 32056-32065 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
|
| Schlagwörter: |
| author_facet |
Aras, Siddhesh Purandare, Neeraja Gladyck, Stephanie Somayajulu-Nitu, Mallika Zhang, Kezhong Wallace, Douglas C. Grossman, Lawrence I. Aras, Siddhesh Purandare, Neeraja Gladyck, Stephanie Somayajulu-Nitu, Mallika Zhang, Kezhong Wallace, Douglas C. Grossman, Lawrence I. |
|---|---|
| author |
Aras, Siddhesh Purandare, Neeraja Gladyck, Stephanie Somayajulu-Nitu, Mallika Zhang, Kezhong Wallace, Douglas C. Grossman, Lawrence I. |
| spellingShingle |
Aras, Siddhesh Purandare, Neeraja Gladyck, Stephanie Somayajulu-Nitu, Mallika Zhang, Kezhong Wallace, Douglas C. Grossman, Lawrence I. Proceedings of the National Academy of Sciences Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms Multidisciplinary |
| author_sort |
aras, siddhesh |
| spelling |
Aras, Siddhesh Purandare, Neeraja Gladyck, Stephanie Somayajulu-Nitu, Mallika Zhang, Kezhong Wallace, Douglas C. Grossman, Lawrence I. 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.2005877117 <jats:title>Significance</jats:title> <jats:p> Pathogenic mtDNA tRNA mutations, such as the 3243A>G MELAS mutation, generally result in multisystem failure. In cybrids harboring ∼70% 3243G mutant mtDNA, the mitochondrial unfolded protein response (UPR <jats:sup>mt</jats:sup> ) is impaired. Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1, or CHCHD2) is a bi-organellar (mitochondrial and nuclear) protein that is reduced in ∼70% 3243G cybrid cells. Under stress conditions, MNRR1 import into mitochondria is impaired, resulting in its preferential concentration in the nucleus. Increased nuclear MNRR1 induces the UPR <jats:sup>mt</jats:sup> through regulation of the ATF5 transcription factor. Overexpression of MNRR1 in ∼70% 3243G cybrid cells induces the UPR <jats:sup>mt</jats:sup> , autophagy, and mitochondrial biogenesis and restores mitochondrial respiratory function; furthermore, the proportion of wild-type mtDNA increases. Thus, MNRR1 overexpression might be beneficial for mtDNA diseases. </jats:p> Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms Proceedings of the National Academy of Sciences |
| doi_str_mv |
10.1073/pnas.2005877117 |
| facet_avail |
Online Free |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjIwMDU4NzcxMTc |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjIwMDU4NzcxMTc |
| institution |
DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Zi4 DE-Gla1 DE-15 DE-Pl11 DE-Rs1 DE-14 DE-105 |
| imprint |
Proceedings of the National Academy of Sciences, 2020 |
| imprint_str_mv |
Proceedings of the National Academy of Sciences, 2020 |
| issn |
0027-8424 1091-6490 |
| issn_str_mv |
0027-8424 1091-6490 |
| language |
English |
| mega_collection |
Proceedings of the National Academy of Sciences (CrossRef) |
| match_str |
aras2020mitochondrialnuclearretrograderegulator1mnrr1rescuesthecellularphenotypeofmelasbyinducinghomeostaticmechanisms |
| publishDateSort |
2020 |
| publisher |
Proceedings of the National Academy of Sciences |
| recordtype |
ai |
| record_format |
ai |
| series |
Proceedings of the National Academy of Sciences |
| source_id |
49 |
| title |
Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_unstemmed |
Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_full |
Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_fullStr |
Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_full_unstemmed |
Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_short |
Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_sort |
mitochondrial nuclear retrograde regulator 1 (mnrr1) rescues the cellular phenotype of melas by inducing homeostatic mechanisms |
| topic |
Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.2005877117 |
| publishDate |
2020 |
| physical |
32056-32065 |
| description |
<jats:title>Significance</jats:title>
<jats:p>
Pathogenic mtDNA tRNA mutations, such as the 3243A>G MELAS mutation, generally result in multisystem failure. In cybrids harboring ∼70% 3243G mutant mtDNA, the mitochondrial unfolded protein response (UPR
<jats:sup>mt</jats:sup>
) is impaired. Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1, or CHCHD2) is a bi-organellar (mitochondrial and nuclear) protein that is reduced in ∼70% 3243G cybrid cells. Under stress conditions, MNRR1 import into mitochondria is impaired, resulting in its preferential concentration in the nucleus. Increased nuclear MNRR1 induces the UPR
<jats:sup>mt</jats:sup>
through regulation of the ATF5 transcription factor. Overexpression of MNRR1 in ∼70% 3243G cybrid cells induces the UPR
<jats:sup>mt</jats:sup>
, autophagy, and mitochondrial biogenesis and restores mitochondrial respiratory function; furthermore, the proportion of wild-type mtDNA increases. Thus, MNRR1 overexpression might be beneficial for mtDNA diseases.
</jats:p> |
| container_issue |
50 |
| container_start_page |
32056 |
| container_title |
Proceedings of the National Academy of Sciences |
| container_volume |
117 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792347218907234305 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T17:51:47.786Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Mitochondrial+Nuclear+Retrograde+Regulator+1+%28MNRR1%29+rescues+the+cellular+phenotype+of+MELAS+by+inducing+homeostatic+mechanisms&rft.date=2020-12-15&genre=article&issn=1091-6490&volume=117&issue=50&spage=32056&epage=32065&pages=32056-32065&jtitle=Proceedings+of+the+National+Academy+of+Sciences&atitle=Mitochondrial+Nuclear+Retrograde+Regulator+1+%28MNRR1%29+rescues+the+cellular+phenotype+of+MELAS+by+inducing+homeostatic+mechanisms&aulast=Grossman&aufirst=Lawrence+I.&rft_id=info%3Adoi%2F10.1073%2Fpnas.2005877117&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792347218907234305 |
| author | Aras, Siddhesh, Purandare, Neeraja, Gladyck, Stephanie, Somayajulu-Nitu, Mallika, Zhang, Kezhong, Wallace, Douglas C., Grossman, Lawrence I. |
| author_facet | Aras, Siddhesh, Purandare, Neeraja, Gladyck, Stephanie, Somayajulu-Nitu, Mallika, Zhang, Kezhong, Wallace, Douglas C., Grossman, Lawrence I., Aras, Siddhesh, Purandare, Neeraja, Gladyck, Stephanie, Somayajulu-Nitu, Mallika, Zhang, Kezhong, Wallace, Douglas C., Grossman, Lawrence I. |
| author_sort | aras, siddhesh |
| container_issue | 50 |
| container_start_page | 32056 |
| container_title | Proceedings of the National Academy of Sciences |
| container_volume | 117 |
| description | <jats:title>Significance</jats:title> <jats:p> Pathogenic mtDNA tRNA mutations, such as the 3243A>G MELAS mutation, generally result in multisystem failure. In cybrids harboring ∼70% 3243G mutant mtDNA, the mitochondrial unfolded protein response (UPR <jats:sup>mt</jats:sup> ) is impaired. Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1, or CHCHD2) is a bi-organellar (mitochondrial and nuclear) protein that is reduced in ∼70% 3243G cybrid cells. Under stress conditions, MNRR1 import into mitochondria is impaired, resulting in its preferential concentration in the nucleus. Increased nuclear MNRR1 induces the UPR <jats:sup>mt</jats:sup> through regulation of the ATF5 transcription factor. Overexpression of MNRR1 in ∼70% 3243G cybrid cells induces the UPR <jats:sup>mt</jats:sup> , autophagy, and mitochondrial biogenesis and restores mitochondrial respiratory function; furthermore, the proportion of wild-type mtDNA increases. Thus, MNRR1 overexpression might be beneficial for mtDNA diseases. </jats:p> |
| doi_str_mv | 10.1073/pnas.2005877117 |
| facet_avail | Online, Free |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjIwMDU4NzcxMTc |
| imprint | Proceedings of the National Academy of Sciences, 2020 |
| imprint_str_mv | Proceedings of the National Academy of Sciences, 2020 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Zi4, DE-Gla1, DE-15, DE-Pl11, DE-Rs1, DE-14, DE-105 |
| issn | 0027-8424, 1091-6490 |
| issn_str_mv | 0027-8424, 1091-6490 |
| language | English |
| last_indexed | 2024-03-01T17:51:47.786Z |
| match_str | aras2020mitochondrialnuclearretrograderegulator1mnrr1rescuesthecellularphenotypeofmelasbyinducinghomeostaticmechanisms |
| mega_collection | Proceedings of the National Academy of Sciences (CrossRef) |
| physical | 32056-32065 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | ai |
| recordtype | ai |
| series | Proceedings of the National Academy of Sciences |
| source_id | 49 |
| spelling | Aras, Siddhesh Purandare, Neeraja Gladyck, Stephanie Somayajulu-Nitu, Mallika Zhang, Kezhong Wallace, Douglas C. Grossman, Lawrence I. 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.2005877117 <jats:title>Significance</jats:title> <jats:p> Pathogenic mtDNA tRNA mutations, such as the 3243A>G MELAS mutation, generally result in multisystem failure. In cybrids harboring ∼70% 3243G mutant mtDNA, the mitochondrial unfolded protein response (UPR <jats:sup>mt</jats:sup> ) is impaired. Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1, or CHCHD2) is a bi-organellar (mitochondrial and nuclear) protein that is reduced in ∼70% 3243G cybrid cells. Under stress conditions, MNRR1 import into mitochondria is impaired, resulting in its preferential concentration in the nucleus. Increased nuclear MNRR1 induces the UPR <jats:sup>mt</jats:sup> through regulation of the ATF5 transcription factor. Overexpression of MNRR1 in ∼70% 3243G cybrid cells induces the UPR <jats:sup>mt</jats:sup> , autophagy, and mitochondrial biogenesis and restores mitochondrial respiratory function; furthermore, the proportion of wild-type mtDNA increases. Thus, MNRR1 overexpression might be beneficial for mtDNA diseases. </jats:p> Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms Proceedings of the National Academy of Sciences |
| spellingShingle | Aras, Siddhesh, Purandare, Neeraja, Gladyck, Stephanie, Somayajulu-Nitu, Mallika, Zhang, Kezhong, Wallace, Douglas C., Grossman, Lawrence I., Proceedings of the National Academy of Sciences, Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms, Multidisciplinary |
| title | Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_full | Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_fullStr | Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_full_unstemmed | Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_short | Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| title_sort | mitochondrial nuclear retrograde regulator 1 (mnrr1) rescues the cellular phenotype of melas by inducing homeostatic mechanisms |
| title_unstemmed | Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1) rescues the cellular phenotype of MELAS by inducing homeostatic mechanisms |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.2005877117 |