神经元 DNA 修复经乙酰胆碱信号维持全身线粒体功能
Neuronal DNA repair mediates systemic mitochondrial maintenance through acetylcholine signaling
研究者在秀丽隐杆线虫中把核苷酸切除修复（NER）活性限定在特定组织，发现组织特异性 DNA 修复就足以提升整体的 DNA 损伤抗性。仅将 NER 活性限定在神经元，在几乎所有受测组织中都能提供与全身 NER 相近的整体 DNA 损伤抗性。作者进一步表明，这种系统性的 DNA 损伤韧性由神经元乙酰胆碱信号介导，该信号促进全身线粒体活性的维持。研究以 NER 突变相关的早衰样综合征为背景，探讨特定细胞类型的 DNA 修复能否对携带 DNA 损伤的其他组织产生非细胞自主影响。
来源：Nucleic Acids Research · doi.org
DNA repair defects such as nucleotide excision repair (NER) mutations can lead to progeroid syndromes characterized by growth retardation and accelerated aging with distinct tissue type specific pathologies. DNA-damage-induced dysfunction of specific cell types can impair the organism’s overall function. It is unknown whether, in reverse, DNA repair in specific tissues can have non-cell-autonomous consequences on other tissues carrying DNA damage. To explore the organismal consequences of cell-type-specific DNA repair, we restricted NER activity to specific tissues and monitored consequences on organismal health in Caenorhabditis elegans. Unexpectedly, we observed that tissue-specific DNA repair is sufficient to improve overall DNA damage resistance. Strikingly, NER activity restricted to neurons only is sufficient to provide similar overall DNA damage resistance as whole-body NER in almost all tissues tested. We show that this systemic DNA damage resilience is mediated by neuronal acetylcholine signaling that promotes the maintenance of mitochondrial activity throughout the organism.