# Auto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan

## TL;DR

A modified enzyme in yeast improves cell lifespan and mimics the effects of calorie restriction by boosting energy metabolism.

## Contribution

Auto-sumoylation of Ubc9 enzyme enhances lifespan and mimics calorie restriction effects in yeast.

## Key findings

- Yeast adapted to Ulp2 loss show increased growth and replicative lifespan with CR-like gene expression.
- Auto-sumoylation of Ubc9 enzyme alters energy metabolism and translation regulation.
- High Ubc9 auto-sumoylation is essential for aged cell survival and lifespan extension.

## Abstract

Calorie restriction (CR) provides anti-aging benefits through diverse processes, such as reduced metabolism and growth and increased mitochondrial activity. Although controversy still exists regarding CR-mediated lifespan effects, many researchers are seeking interventions that mimic the effects of CR. Yeast has proven to be a useful model system for aging studies, including CR effects. We report here that yeast adapted through in vitro evolution to the severe cellular stress caused by loss of the Ulp2 SUMO-specific protease exhibit both enhanced growth rates and replicative lifespan, and they have altered gene expression profiles similar to those observed in CR. Notably, in certain evolved ulp2Δ lines, a dramatic increase in the auto-sumoylation of Ubc9 E2 SUMO-conjugating enzyme results in altered regulation of multiple targets involved in energy metabolism and translation at both transcriptional and post-translational levels. This increase is essential for the survival of aged cells and CR-mediated lifespan extension. Thus, we suggest that high Ubc9 auto-sumoylation exerts potent anti-aging effects by promoting efficient energy metabolism-driven improvements in cell replication abilities. This potential could be therapeutically explored for the development of novel CR-mimetic strategies.