Mitochondrial form and function are closely interlinked in homeostasis and aging. Inhibiting mitochondrial translation is known to increase lifespan in C. elegans, and is accompanied by a fragmented mitochondrial network. However, whether this link between mitochondrial translation and morphology is causal in longevity remains uncharacterized. Here, we show in C. elegans that disrupting mitochondrial network homeostasis by blocking fission or fusion synergizes with reduced mitochondrial translation to prolong lifespan and stimulate stress response such as the mitochondrial unfolded protein response, UPRMT. Conversely, immobilizing the mitochondrial network through a simultaneous disruption of fission and fusion abrogates the lifespan increase induced by mitochondrial translation inhibition. Furthermore, we find that the synergistic effect of inhibiting both mitochondrial translation and dynamics on lifespan, despite stimulating UPRMT, does not require it. Instead, this lifespan-extending synergy is exclusively dependent on the lysosome biogenesis and autophagy transcription factor HLH-30/TFEB. Altogether, our study reveals the mechanistic crosstalk between mitochondrial translation, mitochondrial dynamics, and lysosomal signaling in regulating longevity.

中文翻译：

---

线粒体翻译和动力学通过 HLH-30 协同延长线虫的寿命

线粒体的形式和功能与体内平衡和衰老密切相关。众所周知，抑制线粒体翻译可以延长线虫的寿命，并且伴随着线粒体网络的碎片化。然而，线粒体翻译和形态之间的这种联系是否与长寿有关仍不清楚。在这里，我们在线虫中发现，通过阻断裂变或融合来破坏线粒体网络稳态，与减少线粒体翻译协同作用，以延长寿命并刺激应激反应，例如线粒体未折叠蛋白反应（UPRMT）。相反，通过同时破坏裂变和融合来固定线粒体网络会消除线粒体翻译抑制引起的寿命延长。此外，我们发现，尽管刺激 UPRMT，但抑制线粒体翻译和动力学对寿命的协同作用并不需要它。相反，这种延长寿命的协同作用完全依赖于溶酶体生物发生和自噬转录因子 HLH-30/TFEB。总而言之，我们的研究揭示了线粒体翻译、线粒体动力学和溶酶体信号传导在调节寿命方面的机制串扰。