RT Journal Article
T1 EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation.
A1 Silva, Joana
A1 Aivio, Suvi
A1 Knobel, Philip A
A1 Bailey, Laura J
A1 Casali, Andreu
A1 Vinaixa, Maria
A1 Garcia-Cao, Isabel
A1 Coyaud, Étienne
A1 Jourdain, Alexis A
A1 Pérez-Ferreros, Pablo
A1 Rojas, Ana M
A1 Antolin-Fontes, Albert
A1 Samino-Gené, Sara
A1 Raught, Brian
A1 González-Reyes, Acaimo
A1 Ribas de Pouplana, Lluís
A1 Doherty, Aidan J
A1 Yanes, Oscar
A1 Stracker, Travis H
AB Mitochondria are subcellular organelles that are critical for meeting the bioenergetic and biosynthetic needs of the cell. Mitochondrial function relies on genes and RNA species encoded both in the nucleus and mitochondria, and on their coordinated translation, import and respiratory complex assembly. Here, we characterize EXD2 (exonuclease 3'-5' domain-containing 2), a nuclear-encoded gene, and show that it is targeted to the mitochondria and prevents the aberrant association of messenger RNAs with the mitochondrial ribosome. Loss of EXD2 results in defective mitochondrial translation, impaired respiration, reduced ATP production, increased reactive oxygen species and widespread metabolic abnormalities. Depletion of the Drosophila melanogaster EXD2 orthologue (CG6744) causes developmental delays and premature female germline stem cell attrition, reduced fecundity and a dramatic extension of lifespan that is reversed with an antioxidant diet. Our results define a conserved role for EXD2 in mitochondrial translation that influences development and ageing.
YR 2018
FD 2018-01-15
LK http://hdl.handle.net/10668/12015
UL http://hdl.handle.net/10668/12015
LA en
DS RISalud
RD Apr 10, 2025