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

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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 Stracker
Mitochondria 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 Biology

ISSN

1465-7392

Publisher

Nature Publishing Group

Volume

20

Page range

162-174

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-01-03

First Open Access (FOA) Date

2018-07-15

First Compliant Deposit (FCD) Date

2017-12-19

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