The mitoepigenome responds to stress, suggesting novel mito-nuclear interactions in vertebrates

Autor: John Lees, Fábio Pèrtille, Pia Løtvedt, Per Jensen, Carlos Guerrero Bosagna
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: BMC Genomics, Vol 24, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 1471-2164
DOI: 10.1186/s12864-023-09668-9
Popis: Abstract The mitochondria are central in the cellular response to changing environmental conditions resulting from disease states, environmental exposures or normal physiological processes. Although the influences of environmental stressors upon the nuclear epigenome are well characterized, the existence and role of the mitochondrial epigenome remains contentious. Here, by quantifying the mitochondrial epigenomic response of pineal gland cells to circadian stress, we confirm the presence of extensive cytosine methylation within the mitochondrial genome. Furthermore, we identify distinct epigenetically plastic regions (mtDMRs) which vary in cytosinic methylation, primarily in a non CpG context, in response to stress and in a sex-specific manner. Motifs enriched in mtDMRs contain recognition sites for nuclear-derived DNA-binding factors (ATF4, HNF4A) important in the cellular metabolic stress response, which we found to be conserved across diverse vertebrate taxa. Together, these findings suggest a new layer of mito-nuclear interaction in which the nuclear metabolic stress response could alter mitochondrial transcriptional dynamics through the binding of nuclear-derived transcription factors in a methylation-dependent context.
Databáze: Directory of Open Access Journals
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