| RRC ID |
83980
|
| Author |
Giovannetti M, Rodríguez-Palero MJ, Fabrizio P, Nicolle O, Bedet C, Michaux G, Witting M, Artal-Sanz M, Palladino F.
|
| Title |
SIN-3 transcriptional coregulator maintains mitochondrial homeostasis and polyamine flux.
|
| Journal |
iScience
|
| Abstract |
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.
|
| Volume |
27(5)
|
| Pages |
109789
|
| Published |
2024-5-17
|
| DOI |
10.1016/j.isci.2024.109789
|
| PII |
S2589-0042(24)01011-3
|
| PMID |
38746662
|
| PMC |
PMC11091686
|
| Resource |
| C.elegans |
tm1276 |
