Mitochondrial quality control during inheritance is associated with lifespan and mother–daughter age asymmetry in budding yeast

Abstract

SummaryFluorescence 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 mmr1D 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 mmr1D 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.

Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals “aging factors” and mechanism of lifespan asymmetry

“…One example is extrachromosomal rDNA circles, which are known to be a limiting factor for lifespan (12,13) and are retained in mother cells (14)(15)(16). Protein aggregates, carbonylated proteins, and reactive oxygen species have also been reported to distribute asymmetrically between old mothers and their daughters (17)(18)(19)(20)(21)(22). Preferential retention of membrane transporters in the mother cells has also been associated with lifespan asymmetry (23,24).…”

Programmed Cell Death Initiation and Execution in Budding Yeast

“…In addition, a retrograde actin cable force is present that directs cargo toward the mother. Healthy mitochondria can bind the motors with sufficient strength to navigate to the bud despite the retrograde force moving in the opposite direction (McFaline-Figueroa et al 2011). Pon and coworkers have likened this phenomenon to salmon swimming upstream against the river current (Higuchi et al 2013).…”

“…Both replicative and chronological aging processes in budding yeast are driven by ROS accumulation that ultimately results in PCD (Laun et al 2001;Fabrizio et al 2004;Herker et al 2004). For example, mother cells age through accumulation of oxidatively damaged proteins or mitochondria that are not passed on to their daughters (Aguilaniu et al 2003;McFaline-Figueroa et al 2011). In addition, protein aggregates are retained in aging mothers (Rujano et al 2006;Spokoini et al 2012) thus allowing daughter cells to start with a clean aging slate.…”

Sharing the cell's bounty – organelle inheritance in yeast

“…Moreover, mitochondria are partitioned asymmetrically between mother and daughter cells. Only 'healthy' mitochondria, which contain less reactive oxygen species and are more reducing than mother cell mitochondria, are inherited by the bud (Higuchi et al, 2013;McFaline-Figueroa et al, 2011;Vevea et al, 2013). Actin dynamics and anchorage of mitochondria at the bud tip ensure that mitochondria are segregated according to their functional state (reviewed by Higuchi-Sanabria et al, 2014;Vevea et al, 2014).…”