EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation

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 assembl...

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Detalles Bibliográficos
Autores: Silva, Joana, Aivio, Suvi, Knobel, Philip A., Bailey, Laura J., Casali, Andreu, Vinaixa, Maria, Garcia Cao, Isabel, Coyaud, Étienne, Jourdain, Alexis A., Pérez Ferreros, Pablo, Rojas, Ana M., Antolin Fontes, Albert, Samino Gené, Sara, Raught, Brian, González Reyes, Acaimo, Ribas de Pouplana, Lluís, Doherty, Aidan J., Yanes, Oscar, Stracker, Travis H.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/119822
Acceso en línea:https://hdl.handle.net/2445/119822
Access Level:acceso abierto
Palabra clave:Mitocondris
Drosòfila melanogaster
Homeòstasi
Mitochondria
Drosophila melanogaster
Homeostasis
Descripción
Sumario: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.