Mitochondrial quality control during inheritance is associated with lifespan and mother-daughter age asymmetry in budding yeast.
Aging Cell. 2011 Oct; 10(5):885-95
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Ageing is an accumulation of damaged biomolecules that results in reduced or aberrant function of cells and, ultimately, an organism. During gamete formation, or in asexually propagating species, age must be reversed to make the new organism young. How are old or damaged components recognized and prevented from being passed on to the new organism? McFaline-Figueroa et al. find that, in the rejuvenating asymmetric cell divisions of Saccharomyces cerevisiae, dysfunctional mitochondria are retained in the mother cell to promote fitness and long life of the bud cell.
Important targets of age-accumulated damage are mitochondria, which, when compromised, can generate reactive oxygen species that negatively affect a variety of biomolecules. An essential question is, how are mitochondria selected for or against when organisms undergo rejuvenation? Normal proliferative growth of S. cerevisiae comprises a rejuvenation mechanism, in that ageing-associated components - such as rDNA circles and damaged proteins - are retained in the mother cell, generating a comparatively 'young' bud cell. McFaline-Figueroa et al. test the role of asymmetric mitochondrial segregation in controlling the lifespan of S. cerevisiae, finding that a failure to retain damaged mitochondria in the mother cell reduces the fitness and lifespan of the bud cell. Here, mother-bud mitochondrial asymmetry was detected by differences in superoxide levels and redox potential (and, previously, by membrane potential). An interesting open question is how such metabolic differences are recognized by the mitochondria segregation machinery in the cell. The findings have important implications for sexual reproduction and the almost universal feature of paternal mitochondria elimination from zygotes - are paternal mitochondria also 'old' or damaged and are they recognized by the same features? And there is the question of whether similar mitochondria quality controls function in asymmetric stem cell divisions in various developmental contexts, either to increase the fitness of progeny by making them 'young', or, conversely, to maintain the 'youth' of the stem cell itself.
Cowan C: F1000Prime Recommendation of [McFaline-Figueroa JR et al., Aging Cell 2011, 10(5):885-95]. In F1000Prime, 16 Dec 2011; DOI: 10.3410/f.13409002.14779123. F1000Prime.com/13409002#eval14779123
F1000Prime Recommendations, Dissents and Comments for [McFaline-Figueroa JR et al., Aging Cell 2011, 10(5):885-95]. In F1000Prime, 20 Jun 2013; F1000Prime.com/13409002
Uttam Surana 02 Mar 2010
Fluorescence loss in photobleaching experiments and analysis of mitochondrial function using superoxide and redox potential biosensors revealed that mitochondria within individual yeast cells are physically and functionally distinct. Mitochondria that are retained in mother cells during yeast cell division have a significantly more oxidizing redox potential and higher superoxide levels compared to mitochondria in buds. Retention of mitochondria with more oxidizing redox potential in mother cells occurs to the same extent in young and older cells and can account for the age-associated decline in total cellular mitochondrial redox potential in yeast as they age from 0 to 5 generations. Deletion of Mmr1p, a member of the DSL1 family of tethering proteins that localizes to mitochondria at the bud tip and is required for normal mitochondrial inheritance, produces defects in mitochondrial quality control and heterogeneity in replicative lifespan (RLS). Long-lived mmr1Δ cells exhibit prolonged RLS, reduced mean generation times, more reducing mitochondrial redox potential and lower mitochondrial superoxide levels compared to wild-type cells. Short-lived mmr1Δ cells exhibit the opposite phenotypes. Moreover, short-lived cells give rise exclusively to short-lived cells, while the majority of daughters of long-lived cells are long lived. These findings support the model that the mitochondrial inheritance machinery promotes retention of lower-functioning mitochondria in mother cells and that this process contributes to both mother-daughter age asymmetry and age-associated declines in cellular fitness.
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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