Cargando…

Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication

Mitochondrial chaperones have multiple functions that are essential for proper functioning of mitochondria. In the human-pathogenic protist Trypanosoma brucei, we demonstrate a novel function of the highly conserved machinery composed of mitochondrial heat shock proteins 70 and 40 (mtHsp70/mtHsp40)...

Descripción completa

Detalles Bibliográficos
Autores principales: Týč, Jiří, Klingbeil, Michele M., Lukeš, Julius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337576/
https://www.ncbi.nlm.nih.gov/pubmed/25670781
http://dx.doi.org/10.1128/mBio.02425-14
_version_ 1782481085726195712
author Týč, Jiří
Klingbeil, Michele M.
Lukeš, Julius
author_facet Týč, Jiří
Klingbeil, Michele M.
Lukeš, Julius
author_sort Týč, Jiří
collection PubMed
description Mitochondrial chaperones have multiple functions that are essential for proper functioning of mitochondria. In the human-pathogenic protist Trypanosoma brucei, we demonstrate a novel function of the highly conserved machinery composed of mitochondrial heat shock proteins 70 and 40 (mtHsp70/mtHsp40) and the ATP exchange factor Mge1. The mitochondrial DNA of T. brucei, also known as kinetoplast DNA (kDNA), is represented by a single catenated network composed of thousands of minicircles and dozens of maxicircles packed into an electron-dense kDNA disk. The chaperones mtHsp70 and mtHsp40 and their cofactor Mge1 are uniformly distributed throughout the single mitochondrial network and are all essential for the parasite. Following RNA interference (RNAi)-mediated depletion of each of these proteins, the kDNA network shrinks and eventually disappears. Ultrastructural analysis of cells depleted for mtHsp70 or mtHsp40 revealed that the otherwise compact kDNA network becomes severely compromised, a consequence of decreased maxicircle and minicircle copy numbers. Moreover, we show that the replication of minicircles is impaired, although the lack of these proteins has a bigger impact on the less abundant maxicircles. We provide additional evidence that these chaperones are indispensable for the maintenance and replication of kDNA, in addition to their already known functions in Fe-S cluster synthesis and protein import.
format Online
Article
Text
id pubmed-4337576
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher American Society of Microbiology
record_format MEDLINE/PubMed
spelling pubmed-43375762015-02-24 Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication Týč, Jiří Klingbeil, Michele M. Lukeš, Julius mBio Research Article Mitochondrial chaperones have multiple functions that are essential for proper functioning of mitochondria. In the human-pathogenic protist Trypanosoma brucei, we demonstrate a novel function of the highly conserved machinery composed of mitochondrial heat shock proteins 70 and 40 (mtHsp70/mtHsp40) and the ATP exchange factor Mge1. The mitochondrial DNA of T. brucei, also known as kinetoplast DNA (kDNA), is represented by a single catenated network composed of thousands of minicircles and dozens of maxicircles packed into an electron-dense kDNA disk. The chaperones mtHsp70 and mtHsp40 and their cofactor Mge1 are uniformly distributed throughout the single mitochondrial network and are all essential for the parasite. Following RNA interference (RNAi)-mediated depletion of each of these proteins, the kDNA network shrinks and eventually disappears. Ultrastructural analysis of cells depleted for mtHsp70 or mtHsp40 revealed that the otherwise compact kDNA network becomes severely compromised, a consequence of decreased maxicircle and minicircle copy numbers. Moreover, we show that the replication of minicircles is impaired, although the lack of these proteins has a bigger impact on the less abundant maxicircles. We provide additional evidence that these chaperones are indispensable for the maintenance and replication of kDNA, in addition to their already known functions in Fe-S cluster synthesis and protein import. American Society of Microbiology 2015-02-10 /pmc/articles/PMC4337576/ /pubmed/25670781 http://dx.doi.org/10.1128/mBio.02425-14 Text en Copyright © 2015 Týč et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Týč, Jiří
Klingbeil, Michele M.
Lukeš, Julius
Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication
title Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication
title_full Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication
title_fullStr Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication
title_full_unstemmed Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication
title_short Mitochondrial Heat Shock Protein Machinery Hsp70/Hsp40 Is Indispensable for Proper Mitochondrial DNA Maintenance and Replication
title_sort mitochondrial heat shock protein machinery hsp70/hsp40 is indispensable for proper mitochondrial dna maintenance and replication
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337576/
https://www.ncbi.nlm.nih.gov/pubmed/25670781
http://dx.doi.org/10.1128/mBio.02425-14
work_keys_str_mv AT tycjiri mitochondrialheatshockproteinmachineryhsp70hsp40isindispensableforpropermitochondrialdnamaintenanceandreplication
AT klingbeilmichelem mitochondrialheatshockproteinmachineryhsp70hsp40isindispensableforpropermitochondrialdnamaintenanceandreplication
AT lukesjulius mitochondrialheatshockproteinmachineryhsp70hsp40isindispensableforpropermitochondrialdnamaintenanceandreplication