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EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation
journal contribution
posted on 2023-06-09, 09:28 authored by Joana Silva, Suvi Aivio, Philip A Knobel, Laura BaileyLaura Bailey, Andreu Casali, Maria Vinaixa, Isabel Garcia-Cao, Étienne Coyaud, Alexis A Jourdain, Pablo Perez-Ferreros, Ana M Rojas, Albert Antolin-Fontes, Sara Samino-Gené, Brian Raught, Acaimo González-Reyes, Lluis Ribas de Pouplana, Aidan DohertyAidan Doherty, Oscar Yanes, Travis H StrackerMitochondria are subcellular organelles 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, as well as their coordinated translation, import and respiratory complex assembly. Here we describe the characterization of exonuclease domain like 2 (EXD2), a nuclear encoded gene that we show is targeted to the mitochondria and prevents the aberrant association of mRNAs with the mitochondrial ribosome. The loss of EXD2 resulted in defective mitochondrial translation, impaired respiration, reduced ATP production, increased reactive oxygen species and widespread metabolic abnormalities. Depletion of EXD2/CG6744 in D.melanogaster caused developmental delays and premature female germline stem cell attrition, reduced fecundity and a dramatic extension of lifespan that could be reversed with an anti-oxidant diet. Our results define a conserved role for EXD2 in mitochondrial translation that influences development and aging.
Funding
Understanding the role of PrimPol in damage tolerance during genome replication in eukaryotic cells; G1621; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/M008800/1
The role of a novel family of eukaryotic DNA polymerases in mitochondrial DNA replication; G0207; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/H019723/1
History
Publication status
- Published
File Version
- Accepted version
Journal
Nature Cell BiologyISSN
1465-7392Publisher
Nature Publishing GroupExternal DOI
Volume
20Page range
162-174Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-01-03First Open Access (FOA) Date
2018-07-15First Compliant Deposit (FCD) Date
2017-12-19Usage metrics
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