Cargando…
Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling
Mitochondrial fission facilitates cytochrome c release from the intracristae space into the cytoplasm during intrinsic apoptosis, although how the mitochondrial fission factor Drp1 and its mitochondrial receptors Mff, MiD49, and MiD51 are involved in this reaction remains elusive. Here, we analyzed...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772499/ https://www.ncbi.nlm.nih.gov/pubmed/26903540 http://dx.doi.org/10.1083/jcb.201508099 |
_version_ | 1782418581740322816 |
---|---|
author | Otera, Hidenori Miyata, Non Kuge, Osamu Mihara, Katsuyoshi |
author_facet | Otera, Hidenori Miyata, Non Kuge, Osamu Mihara, Katsuyoshi |
author_sort | Otera, Hidenori |
collection | PubMed |
description | Mitochondrial fission facilitates cytochrome c release from the intracristae space into the cytoplasm during intrinsic apoptosis, although how the mitochondrial fission factor Drp1 and its mitochondrial receptors Mff, MiD49, and MiD51 are involved in this reaction remains elusive. Here, we analyzed the functional division of these receptors with their knockout (KO) cell lines. In marked contrast to Mff-KO cells, MiD49/MiD51-KO and Drp1-KO cells completely resisted cristae remodeling and cytochrome c release during apoptosis. This phenotype in MiD49/51-KO cells, but not Drp1-KO cells, was completely abolished by treatments disrupting cristae structure such as OPA1 depletion. Unexpectedly, OPA1 oligomers generally thought to resist cytochrome c release by stabilizing the cristae structure were similarly disassembled in Drp1-KO and MiD49/51-KO cells, indicating that disassembly of OPA1 oligomers is not directly linked to cristae remodeling for cytochrome c release. Together, these results indicate that Drp1-dependent mitochondrial fission through MiD49/MiD51 regulates cristae remodeling during intrinsic apoptosis. |
format | Online Article Text |
id | pubmed-4772499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47724992016-08-29 Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling Otera, Hidenori Miyata, Non Kuge, Osamu Mihara, Katsuyoshi J Cell Biol Research Articles Mitochondrial fission facilitates cytochrome c release from the intracristae space into the cytoplasm during intrinsic apoptosis, although how the mitochondrial fission factor Drp1 and its mitochondrial receptors Mff, MiD49, and MiD51 are involved in this reaction remains elusive. Here, we analyzed the functional division of these receptors with their knockout (KO) cell lines. In marked contrast to Mff-KO cells, MiD49/MiD51-KO and Drp1-KO cells completely resisted cristae remodeling and cytochrome c release during apoptosis. This phenotype in MiD49/51-KO cells, but not Drp1-KO cells, was completely abolished by treatments disrupting cristae structure such as OPA1 depletion. Unexpectedly, OPA1 oligomers generally thought to resist cytochrome c release by stabilizing the cristae structure were similarly disassembled in Drp1-KO and MiD49/51-KO cells, indicating that disassembly of OPA1 oligomers is not directly linked to cristae remodeling for cytochrome c release. Together, these results indicate that Drp1-dependent mitochondrial fission through MiD49/MiD51 regulates cristae remodeling during intrinsic apoptosis. The Rockefeller University Press 2016-02-29 /pmc/articles/PMC4772499/ /pubmed/26903540 http://dx.doi.org/10.1083/jcb.201508099 Text en © 2016 Otera et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Otera, Hidenori Miyata, Non Kuge, Osamu Mihara, Katsuyoshi Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling |
title | Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling |
title_full | Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling |
title_fullStr | Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling |
title_full_unstemmed | Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling |
title_short | Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling |
title_sort | drp1-dependent mitochondrial fission via mid49/51 is essential for apoptotic cristae remodeling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772499/ https://www.ncbi.nlm.nih.gov/pubmed/26903540 http://dx.doi.org/10.1083/jcb.201508099 |
work_keys_str_mv | AT oterahidenori drp1dependentmitochondrialfissionviamid4951isessentialforapoptoticcristaeremodeling AT miyatanon drp1dependentmitochondrialfissionviamid4951isessentialforapoptoticcristaeremodeling AT kugeosamu drp1dependentmitochondrialfissionviamid4951isessentialforapoptoticcristaeremodeling AT miharakatsuyoshi drp1dependentmitochondrialfissionviamid4951isessentialforapoptoticcristaeremodeling |