Showing papers by "Daniel E. Gottschling published in 2012"
TL;DR: It is found that vacuolar acidity declines during the early asymmetric divisions of a mother cell, and that preventing this decline suppresses mitochondrial dysfunction and extends lifespan, and a potentially conserved mechanism by which calorie restriction delays the ageing process is outlined.
Abstract: Mitochondria have a central role in ageing. They are considered to be both a target of the ageing process and a contributor to it. Alterations in mitochondrial structure and function are evident during ageing in most eukaryotes, but how this occurs is poorly understood. Here we identify a functional link between the lysosome-like vacuole and mitochondria in Saccharomyces cerevisiae, and show that mitochondrial dysfunction in replicatively aged yeast arises from altered vacuolar pH. We found that vacuolar acidity declines during the early asymmetric divisions of a mother cell, and that preventing this decline suppresses mitochondrial dysfunction and extends lifespan. Surprisingly, changes in vacuolar pH do not limit mitochondrial function by disrupting vacuolar protein degradation, but rather by reducing pH-dependent amino acid storage in the vacuolar lumen. We also found that calorie restriction promotes lifespan extension at least in part by increasing vacuolar acidity via conserved nutrient-sensing pathways. Interestingly, although vacuolar acidity is reduced in aged mother cells, acidic vacuoles are regenerated in newborn daughters, coinciding with daughter cells having a renewed lifespan potential. Overall, our results identify vacuolar pH as a critical regulator of ageing and mitochondrial function, and outline a potentially conserved mechanism by which calorie restriction delays the ageing process. Because the functions of the vacuole are highly conserved throughout evolution, we propose that lysosomal pH may modulate mitochondrial function and lifespan in other eukaryotic cells.
468 citations
TL;DR: A cytoplasmic protein delivers iron-sulfur clusters to nuclear proteins that function in DNA replication and repair to enzymes that maintain genome integrity.
Abstract: When an important, fragile package needs to be delivered with high assurance, a dependable envoy can ensure that it lands in the right hands. Iron-sulfur (Fe-S) clusters are one such package in the cell. Many proteins, including some that replicate and maintain the nuclear genome, require them. Two papers in this issue—by Gari et al. ( 1 ) on page 243 and Stehling et al. ( 2 ) on page 195—identify MMS19 as the envoy that delivers Fe-S clusters to enzymes that maintain genome integrity.
7 citations