A genetic construct preserved fatty acid synthesis during AMPK activation and supported the growth of old yeast cells

A genetic construct preserved fatty acid synthesis during AMPK activation and supported the growth of old yeast cells

On July 31, eLife published a study on budding yeast. The authors constitutively activated the energy regulator AMPK while protecting Acc1, the enzyme that initiates fatty acid synthesis, from inhibition by AMPK.

In budding yeast, a mother cell produces daughter cells. During their final divisions, many mother cells begin to divide more slowly. The authors refer to this late decline as senescence. They examined why cells of the same age reach this state through different paths.

AMPK reorganizes cellular metabolism when energy is scarce. Constitutive AMPK activation reduced signs of senescence in about half of the aging population. These cells required the transport of cytosolic acetyl-CoA into mitochondria.

In another part of the population, the same signal inhibited Acc1. As a result, the cells synthesized fewer fatty acids, which provide material for membranes and serve as an energy reserve. AMPK helped one group of old cells but restricted lipid production in another.

The authors combined constitutive AMPK activation with a substitution in Acc1. The A2A construct prevented AMPK from inactivating this enzyme. After 48 hours, A2A cells were more likely than cells with activated AMPK alone to combine a low level of the senescence marker with a high number of bud scars. In this yeast system, active AMPK and functional Acc1 preserved division in old cells.

In a separate experiment, viable old A2A cells formed colonies within one day that were almost the same size as those formed by young cells from the same strain. The authors separated two effects of the same signal: AMPK remained active, while fatty acid synthesis continued.