Universität zu Köln

Bonekamp, Nina A., Jiang, Min, Motori, Elisa, Villegas, Rodolfo Garcia, Koolmeister, Camilla, Atanassov, Ilian, Mesaros, Andrea, Park, Chan Bae and Larsson, Nils-Goran ORCID: 0000-0001-5100-996X (2021). High levels of TFAM repress mammalian mitochondrial DNA transcription in vivo. Life Sci. Alliance, 4 (11). COLD SPRING HARBOR: LIFE SCIENCE ALLIANCE LLC. ISSN 2575-1077

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Abstract

Mitochondrial transcription factor A (TFAM) is compacting mitochondrial DNA (dmtDNA) into nucleoids and directly controls mtDNA copy number. Here, we show that the TFAM-to-mtDNA ratio is critical for maintaining normal mtDNA expression in different mouse tissues. Moderately increased TFAM protein levels increase mtDNA copy number but a normal TFAM-to-mtDNA ratio is maintained resulting in unaltered mtDNA expression and normal whole animal metabolism. Mice ubiquitously expressing very high TFAM levels develop pathology leading to deficient oxidative phosphorylation (OXPHOS) and early postnatal lethality. The TFAM-to-mtDNA ratio varies widely between tissues in these mice and is very high in skeletal muscle leading to strong repression of mtDNA expression and OXPHOS deficiency. In the heart, increased mtDNA copy number results in a near normal TFAM-to-mtDNA ratio and maintained OXPHOS capacity. In liver, induction of LONP1 protease and mitochondrial RNA polymerase expression counteracts the silencing effect of high TFAM levels. TFAM thus acts as a general repressor of mtDNA expression and this effect can be counterbalanced by tissue-specific expression of regulatory factors.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bonekamp, Nina A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jiang, Min UNSPECIFIED UNSPECIFIED UNSPECIFIED Motori, Elisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Villegas, Rodolfo Garcia UNSPECIFIED UNSPECIFIED UNSPECIFIED Koolmeister, Camilla UNSPECIFIED UNSPECIFIED UNSPECIFIED Atanassov, Ilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mesaros, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Park, Chan Bae UNSPECIFIED UNSPECIFIED UNSPECIFIED Larsson, Nils-Goran UNSPECIFIED orcid.org/0000-0001-5100-996X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-593872
DOI:	10.26508/lsa.202101034
Journal or Publication Title:	Life Sci. Alliance
Volume:	4
Number:	11
Date:	2021
Publisher:	LIFE SCIENCE ALLIANCE LLC
Place of Publication:	COLD SPRING HARBOR
ISSN:	2575-1077
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MTDNA COPY NUMBER; FACTOR-A TFAM; RNA-POLYMERASE; OVEREXPRESSION; MAINTENANCE; EXPRESSION; NUCLEOIDS; PROTEIN; BIOGENESIS; ACTIVATION Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59387