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

Silva, Joana, Aivio, Suvi, Knobel, Philip A, Bailey, Laura, Casali, Andreu, Vinaixa, Maria, Garcia-Cao, Isabel, Coyaud, Étienne, Jourdain, Alexis A, Perez-Ferreros, Pablo, Rojas, Ana M, Antolin-Fontes, Albert, Samino-Gené, Sara, Raught, Brian, González-Reyes, Acaimo, Ribas de Pouplana, Lluis, Doherty, Aidan J, Yanes, Oscar and Stracker, Travis H (2018) EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation. Nature Cell Biology, 20. pp. 162-174. ISSN 1465-7392

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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.

Item Type: Article
Keywords: metabolism, respiration, EXD2, OXPHOS, stem cell, lifespan
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Aidan Doherty
Date Deposited: 03 Jan 2018 14:06
Last Modified: 18 Jul 2019 14:00
URI: http://sro.sussex.ac.uk/id/eprint/72341

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Project NameSussex Project NumberFunderFunder Ref
The role of a novel family of eukaryotic DNA polymerases in mitochondrial DNA replicationG0207BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/H019723/1
Understanding the role of PrimPol in damage tolerance during genome replication in eukaryotic cellsG1621BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/M008800/1