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SIN-3 transcriptional coregulator maintains mitochondrial homeostasis and polyamine flux.
iScience 27:109789 (2024)
Mitochondrial function relies on the coordinated transcription of mitochondrial and nuclear genomes to assemble respiratory chain complexes. Across species, the SIN3 coregulator influences mitochondrial functions, but how its loss impacts mitochondrial homeostasis and metabolism in the context of a whole organism is unknown. Exploring this link is important because SIN3 haploinsufficiency causes intellectual disability/autism syndromes and SIN3 plays a role in tumor biology. Here we show that loss of C. elegans SIN-3 results in transcriptional deregulation of mitochondrial- and nuclear-encoded mitochondrial genes, potentially leading to mito-nuclear imbalance. Consistent with impaired mitochondrial function, sin-3 mutants show extensive mitochondrial fragmentation by transmission electron microscopy (TEM) and in vivo imaging, and altered oxygen consumption. Metabolomic analysis of sin-3 mutant animals revealed a mitochondria stress signature and deregulation of methionine flux, resulting in decreased S-adenosyl methionine (SAM) and increased polyamine levels. Our results identify SIN3 as a key regulator of mitochondrial dynamics and metabolic flux, with important implications for human pathologies.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cell Biology ; Omics ; Systems Biology; Caenorhabditis-elegans; Life-span; Ornithine-decarboxylase; Stress-response; Metabolism; Dynamics; Complex; Genes; Haploinsufficiency; Resistance
ISSN (print) / ISBN
2589-0042
e-ISSN
2589-0042
Journal
iScience
Quellenangaben
Volume: 27,
Issue: 5,
Article Number: 109789
Publisher
Elsevier
Publishing Place
Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Metabolomics & Proteomics (CF-MPC)
Grants
Universite de Rennes
French National Research Agency
Centre National de la Recherche Scientifique
Ministerio de Ciencia, Innovacion y Universidades, the Agencia Estatal de Investigacion (AEI)
ANR (Agence Nationale de la Recherche)
French National Research Agency
Centre National de la Recherche Scientifique
Ministerio de Ciencia, Innovacion y Universidades, the Agencia Estatal de Investigacion (AEI)
ANR (Agence Nationale de la Recherche)