TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts
The correct organization of mitochondrial DNA (mtDNA) in nucleoids and the contacts of mitochondria with the ER play an important role in maintaining the mitochondrial genome distribution within the cell. Mitochondria-associated ER membranes (MAMs) consist of interacting proteins and lipids located...
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doaj-39426409ccb144888c9438378921349f2021-09-25T05:09:04ZengElsevierBiochemistry and Biophysics Reports2405-58082021-12-0128101142TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contactsKoit Aasumets0Yuliya Basikhina1Jaakko L. Pohjoismäki2Steffi Goffart3Joachim Gerhold4Institute of Technology, University of Tartu, Nooruse 1, 50411, Tartu, Estonia; Corresponding author.Faculty of Medicine and Health Technology, Tampere University, FI-33014, FinlandDepartment of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, FI 80101, Joensuu, FinlandDepartment of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, FI 80101, Joensuu, FinlandInstitute of Technology, University of Tartu, Nooruse 1, 50411, Tartu, EstoniaThe correct organization of mitochondrial DNA (mtDNA) in nucleoids and the contacts of mitochondria with the ER play an important role in maintaining the mitochondrial genome distribution within the cell. Mitochondria-associated ER membranes (MAMs) consist of interacting proteins and lipids located in the outer mitochondrial membrane and ER membrane, forming a platform for the mitochondrial inner membrane-associated genome replication factory as well as connecting the nucleoids with the mitochondrial division machinery. We show here that knockdown of a core component of mitochondrial nucleoids, TFAM, causes changes in the mitochondrial nucleoid populations, which subsequently impact ER-mitochondria membrane contacts. Knockdown of TFAM causes a significant decrease in the copy number of mtDNA as well as aggregation of mtDNA nucleoids. At the same time, it causes significant upregulation of the replicative TWNK helicase in the membrane-associated nucleoid fraction. This is accompanied by a transient elevation of MAM proteins, indicating a rearrangement of the linkage between ER and mitochondria triggered by changes in mitochondrial nucleoids. Reciprocal knockdown of the mitochondrial replicative helicase TWNK causes a decrease in mtDNA copy number and modifies mtDNA membrane association, however, it does not cause nucleoid aggregation and considerable alterations of MAM proteins in the membrane-associated fraction. Our explanation is that the aggregation of mitochondrial nucleoids resulting from TFAM knockdown triggers a compensatory mechanism involving the reorganization of both mitochondrial nucleoids and MAM. These results could provide an important insight into pathological conditions associated with impaired nucleoid organization or defects of mtDNA distribution.http://www.sciencedirect.com/science/article/pii/S2405580821002363Mitochondrial DNANucleoidsMitochondrial transcription factor A (TFAM)Organellar membranesTWNK helicase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Koit Aasumets Yuliya Basikhina Jaakko L. Pohjoismäki Steffi Goffart Joachim Gerhold |
spellingShingle |
Koit Aasumets Yuliya Basikhina Jaakko L. Pohjoismäki Steffi Goffart Joachim Gerhold TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts Biochemistry and Biophysics Reports Mitochondrial DNA Nucleoids Mitochondrial transcription factor A (TFAM) Organellar membranes TWNK helicase |
author_facet |
Koit Aasumets Yuliya Basikhina Jaakko L. Pohjoismäki Steffi Goffart Joachim Gerhold |
author_sort |
Koit Aasumets |
title |
TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts |
title_short |
TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts |
title_full |
TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts |
title_fullStr |
TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts |
title_full_unstemmed |
TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts |
title_sort |
tfam knockdown-triggered mtdna-nucleoid aggregation and a decrease in mtdna copy number induce the reorganization of nucleoid populations and mitochondria-associated er-membrane contacts |
publisher |
Elsevier |
series |
Biochemistry and Biophysics Reports |
issn |
2405-5808 |
publishDate |
2021-12-01 |
description |
The correct organization of mitochondrial DNA (mtDNA) in nucleoids and the contacts of mitochondria with the ER play an important role in maintaining the mitochondrial genome distribution within the cell. Mitochondria-associated ER membranes (MAMs) consist of interacting proteins and lipids located in the outer mitochondrial membrane and ER membrane, forming a platform for the mitochondrial inner membrane-associated genome replication factory as well as connecting the nucleoids with the mitochondrial division machinery. We show here that knockdown of a core component of mitochondrial nucleoids, TFAM, causes changes in the mitochondrial nucleoid populations, which subsequently impact ER-mitochondria membrane contacts. Knockdown of TFAM causes a significant decrease in the copy number of mtDNA as well as aggregation of mtDNA nucleoids. At the same time, it causes significant upregulation of the replicative TWNK helicase in the membrane-associated nucleoid fraction. This is accompanied by a transient elevation of MAM proteins, indicating a rearrangement of the linkage between ER and mitochondria triggered by changes in mitochondrial nucleoids. Reciprocal knockdown of the mitochondrial replicative helicase TWNK causes a decrease in mtDNA copy number and modifies mtDNA membrane association, however, it does not cause nucleoid aggregation and considerable alterations of MAM proteins in the membrane-associated fraction. Our explanation is that the aggregation of mitochondrial nucleoids resulting from TFAM knockdown triggers a compensatory mechanism involving the reorganization of both mitochondrial nucleoids and MAM. These results could provide an important insight into pathological conditions associated with impaired nucleoid organization or defects of mtDNA distribution. |
topic |
Mitochondrial DNA Nucleoids Mitochondrial transcription factor A (TFAM) Organellar membranes TWNK helicase |
url |
http://www.sciencedirect.com/science/article/pii/S2405580821002363 |
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