|Mitochondria, metabolism, and aging in yeast|
Topics in Current Genetics (2003)
Category: aging ¤ Added: Jun 11, 2004 ¤ Rating: ◊◊
Quantitative and qualitative changes in metabolism take place when the lifespan is extended in yeast either by genetic or nutritional manipulation. In particular, remodeling of mitochondrial function occurs, and the relationship between this organelle and other cellular compartments moves to the fore. Two separate pathways, the retrograde response and calorie restriction, operate as metabolic mechanisms for life extension in yeast. Though distinct, they share common longevity effectors. The retrograde response is a compensatory measure for mitochondrial dysfunction, while calorie restriction is proposed to be a preventive response. The critical common feature in both appears to be the enhancement of the production of biosynthetic precursors for growth by the mitochondrial Krebs cycle and by the alternate glyoxylate cycle. The communication between the mitochondrion and other cellular compartments that is essential for delivery of these precursors is dependent on the maintenance of a sufficient mitochondrial membrane potential, which declines with age. In actively respiring cells, the transport of biosynthetic precursors is likely to fulfill an additional role. It can uncouple the mitochondria and thus lower the production of reactive oxygen species, which can cause deleterious age changes. When metabolic rates are low, this uncoupling mechanism would control the rate of respiration, while at higher metabolic rates ATP demand becomes dominant. It is likely that the essence of the role of mitochondrial function in aging summarized here is preserved across phyla.