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Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation
The human mitochondrial outer membrane is biophysically unique as it is the only membrane possessing transmembrane β-barrel proteins (mitochondrial outer membrane proteins, mOMPs) in the cell. The most vital of the three mOMPs is the core protein of the translocase of the outer mitochondrial membran...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052162/ https://www.ncbi.nlm.nih.gov/pubmed/35346689 http://dx.doi.org/10.1016/j.jbc.2022.101870 |
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author | Sayyed, Ulfat Mohd. Hanif Mahalakshmi, Radhakrishnan |
author_facet | Sayyed, Ulfat Mohd. Hanif Mahalakshmi, Radhakrishnan |
author_sort | Sayyed, Ulfat Mohd. Hanif |
collection | PubMed |
description | The human mitochondrial outer membrane is biophysically unique as it is the only membrane possessing transmembrane β-barrel proteins (mitochondrial outer membrane proteins, mOMPs) in the cell. The most vital of the three mOMPs is the core protein of the translocase of the outer mitochondrial membrane (TOM) complex. Identified first as MOM38 in Neurospora in 1990, the structure of Tom40, the core 19-stranded β-barrel translocation channel, was solved in 2017, after nearly three decades. Remarkably, the past four years have witnessed an exponential increase in structural and functional studies of yeast and human TOM complexes. In addition to being conserved across all eukaryotes, the TOM complex is the sole ATP-independent import machinery for nearly all of the ∼1000 to 1500 known mitochondrial proteins. Recent cryo-EM structures have provided detailed insight into both possible assembly mechanisms of the TOM core complex and organizational dynamics of the import machinery and now reveal novel regulatory interplay with other mOMPs. Functional characterization of the TOM complex using biochemical and structural approaches has also revealed mechanisms for substrate recognition and at least five defined import pathways for precursor proteins. In this review, we discuss the discovery, recently solved structures, molecular function, and regulation of the TOM complex and its constituents, along with the implications these advances have for alleviating human diseases. |
format | Online Article Text |
id | pubmed-9052162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-90521622022-05-03 Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation Sayyed, Ulfat Mohd. Hanif Mahalakshmi, Radhakrishnan J Biol Chem JBC Reviews The human mitochondrial outer membrane is biophysically unique as it is the only membrane possessing transmembrane β-barrel proteins (mitochondrial outer membrane proteins, mOMPs) in the cell. The most vital of the three mOMPs is the core protein of the translocase of the outer mitochondrial membrane (TOM) complex. Identified first as MOM38 in Neurospora in 1990, the structure of Tom40, the core 19-stranded β-barrel translocation channel, was solved in 2017, after nearly three decades. Remarkably, the past four years have witnessed an exponential increase in structural and functional studies of yeast and human TOM complexes. In addition to being conserved across all eukaryotes, the TOM complex is the sole ATP-independent import machinery for nearly all of the ∼1000 to 1500 known mitochondrial proteins. Recent cryo-EM structures have provided detailed insight into both possible assembly mechanisms of the TOM core complex and organizational dynamics of the import machinery and now reveal novel regulatory interplay with other mOMPs. Functional characterization of the TOM complex using biochemical and structural approaches has also revealed mechanisms for substrate recognition and at least five defined import pathways for precursor proteins. In this review, we discuss the discovery, recently solved structures, molecular function, and regulation of the TOM complex and its constituents, along with the implications these advances have for alleviating human diseases. American Society for Biochemistry and Molecular Biology 2022-03-26 /pmc/articles/PMC9052162/ /pubmed/35346689 http://dx.doi.org/10.1016/j.jbc.2022.101870 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | JBC Reviews Sayyed, Ulfat Mohd. Hanif Mahalakshmi, Radhakrishnan Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation |
title | Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation |
title_full | Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation |
title_fullStr | Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation |
title_full_unstemmed | Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation |
title_short | Mitochondrial protein translocation machinery: From TOM structural biogenesis to functional regulation |
title_sort | mitochondrial protein translocation machinery: from tom structural biogenesis to functional regulation |
topic | JBC Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052162/ https://www.ncbi.nlm.nih.gov/pubmed/35346689 http://dx.doi.org/10.1016/j.jbc.2022.101870 |
work_keys_str_mv | AT sayyedulfatmohdhanif mitochondrialproteintranslocationmachineryfromtomstructuralbiogenesistofunctionalregulation AT mahalakshmiradhakrishnan mitochondrialproteintranslocationmachineryfromtomstructuralbiogenesistofunctionalregulation |