MON-2, a Golgi protein, mediates autophagy-dependent longevity in Caen…

■ Abstract

The Golgi apparatus plays a central role in trafficking cargoes such as proteins and lipids. Defects in the Golgi

apparatus lead to various diseases, but its role in organismal longevity is largely unknown. Using a quantitative

proteomic approach, we found that a Golgi protein, MON-2, was up-regulated in long-lived Caenorhabditis elegans

mutants with mitochondrial respiration defects and was required for their longevity. Similarly, we showed that

DOP1/PAD-1, which acts with MON-2 to traffic macromolecules between the Golgi and endosome, contributed to

the longevity of respiration mutants. Furthermore, we demonstrated that MON-2 was required for up-regulation of

autophagy, a longevity-associated recycling process, by activating the Atg8 ortholog GABARAP/LGG-1 in C. elegans.

Consistently, we showed that mammalian MON2 activated GABARAPL2 through physical interaction, which increased

autophagic flux in mammalian cells. Thus, the evolutionarily conserved role of MON2 in trafficking between

the Golgi and endosome is an integral part of autophagy-mediated longevity.