Reference : Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans ...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30.
Liu, Yasmine J. [> >]
McIntyre, Rebecca L. [> >]
Janssens, Georges E. [> >]
Williams, Evan mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Lan, Jiayi [> >]
van Weeghel, Michel [> >]
Schomakers, Bauke [> >]
van der Veen, Henk [> >]
van der Wel, Nicole N. [> >]
Yao, Pallas [> >]
Mair, William B. [> >]
Aebersold, Ruedi [> >]
MacInnes, Alyson W. [> >]
Houtkooper, Riekelt H. [> >]
The Journal of cell biology
Yes (verified by ORBilu)
United States
[en] 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.
(c) 2020 Liu et al.

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