Actin Dynamics Affect Mitochondrial Quality Control and Aging in Budding Yeast

Abstract

Summary Actin cables of budding yeast are bundles of F-actin that extend from the bud tip or neck to the mother cell tip, serve as tracks for bidirectional cargo transport, and undergo continuous movement from buds towards mother cells [1]. This movement, retrograde actin cable flow (RACF), is similar to retrograde actin flow in lamellipodia, growth cones, immunological synapses, dendritic spines and filopodia [2–5]. In all cases, actin flow is driven by the push of actin polymerization and assembly at the cell cortex, and myosin-driven pulling forces deeper within the cell [6–10]. Therefore, for movement and inheritance from mothers to buds, mitochondria must “swim upstream” against the opposing force of RACF [11]. We find that increasing RACF rates results in increased fitness of mitochondria inherited by buds, and that the increase in mitochondrial fitness leads to extended replicative lifespan and increased cellular healthspan. The sirtuin SIR2 is required for normal RACF and mitochondrial fitness, and increasing RACF rates in sir2Δ cells increases mitochondrial fitness and cellular healthspan but does not affect replicative lifespan. These studies support the model that RACF serves as a filter for segregation of fit from less fit mitochondria during inheritance, which controls celllular lifespan and healthspan. They also support a role for Sir2p in these processes.

Requirement of Phosphoinositides Containing Stearic Acid To Control Cell Polarity

“…In either the haploid or the diploid context, the number of cables detected per mother cell decreased in strains from which the PSI1 gene was deleted, and the number of mother cells with detectable cables was significantly reduced for mutant strains compared to the number for the WT strain (Table 1), which displayed values in agreement with those from previous work (50). The decreased number of actin cables per cell and the decreased number of cells with detectable actin cables in psi1⌬ strains suggest that cable polymerization was strongly affected in these mutants.…”

When stem cells grow old: phenotypes and mechanisms of stem cell aging

“…budding yeast, wherein damaged DNA, replicating circular DNA, carbonylated proteins and damaged organelles are sequestered, in this case in the mother cell, so that the daughter cell remains youthful (Aguilaniu et al, 2003;Higuchi et al, 2013;Lindner et al, 2008;Sinclair and Guarente, 1997). In animals, the most well-known example of such asymmetric distribution is the 'immortal strand hypothesis', where the parental strand of DNA is sequestered in the daughter stem cell, whereas the strand synthesized during S phase, which might contain errors from replication, is directed to the differentiating daughter cell (Cairns, 1975).…”

Programmed Cell Death Initiation and Execution in Budding Yeast

“…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). This Figure 1 Sources of reactive oxygen species (ROS).…”