Hughes & Gottschling 2012, vacuolar pH limits mitochondrial function and lifespan in yeast.

Reading note on Hughes & Gottschling 2012, Nature, An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast.

HG12 found normal mitochondrial fragmentation was present early in 86% of the cells at 8 divisions, and progressed to large aggregates and small fragments in 93% of cells at 17 divisions for a strain with median lifespan of 28 divisions. This indicates that mitochondrial morphological change occurs  before the dye-off phase around the media lifespan (dramatic drop of viability).

HG12 over-expressed 250 genes that can influence mitochondrial function and screen for mutants can delay the onset of mitochondrial morphological changes during aging, using the mother cell enrichment systems. HG12 also stated that vacoular pH decreases before mitochondrial dysfunction .

Over-expression of VMA1 and AVT1 extended replicative lifespan (Figure 2d, 3d).

Calorie restriction can hold down vacuolar pH and extends replicative lifespan. It looks like that CR mostly shift the survivor curves to the right, meaning influencing the intitial mortality rate.

HG12 proposed that vauolar pH regulate the level of cytoplasmic amino acid levels, and in turn regulate mitochondrial morphology (Supplementary figure 1).

Another short article by Schmidt and Kennedy in Current Biology argued for alternative explanations:  Vacuolar pH influences cytosolic pH and then acts on mitochondrial membrane potential, or go through other genes like TOR1, RTG and Gcn4 to nucleus and then on mitochondria.