Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30

Published on Jun 1, 2020in Journal of Cell Biology8.891
· DOI :10.1083/JCB.201907067
Yasmine J. Liu2
Estimated H-index: 2
(UvA: University of Amsterdam),
Rebecca L. McIntyre1
Estimated H-index: 1
(UvA: University of Amsterdam)
+ 11 AuthorsPallas Yao1
Estimated H-index: 1
(Harvard University)
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.
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: In this issue, Liu et al. (2019. J. Cell. Biol. find that the inhibition of mitochondrial ribosomes in combination with impaired mitochondrial fission or fusion increases C. elegans lifespan by activating the transcription factor HLH-30, which promotes lysosomal biogenesis.