Silva 2018 Nat Cell Biol
|Silva J, Aivio S, Knobel PA, Bailey LJ, Casali A, Vinaixa M, Garcia-Cao I, Coyaud É, Jourdain AA, Pérez-Ferreros P, Rojas AM, Antolin-Fontes A, Samino-Gené S, Raught B, González-Reyes A, Ribas de Pouplana L, Doherty AJ, Yanes O, Stracker TH (2018) EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation. Nat Cell Biol 20:162-74.|
Silva J, Aivio S, Knobel PA, Bailey LJ, Casali A, Vinaixa M, Garcia-Cao I, Coyaud E, Jourdain AA, Perez-Ferreros P, Rojas AM, Antolin-Fontes A, Samino-Gene S, Raught B, Gonzalez-Reyes A, Ribas de Pouplana L, Doherty AJ, Yanes O, Stracker TH (2018) Nat Cell Biol
Abstract: 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.
• Bioblast editor: Kandolf G
Labels: MiParea: Respiration Pathology: Aging;senescence
Tissue;cell: Islet cell;pancreas;thymus Preparation: Permeabilized tissue
Coupling state: OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k