Academic journal article Genetics

Multiple Pathways Influence Mitochondrial Inheritance in Budding Yeast

Academic journal article Genetics

Multiple Pathways Influence Mitochondrial Inheritance in Budding Yeast

Article excerpt

ABSTRACT

Yeast mitochondria form a branched tubular network. Mitochondrial inheritance is tightly coupled with bud emergence, ensuring that daughter cells receive mitochondria from mother cells during division. Proteins reported to influence mitochondrial inheritance include the mitochondrial rho (Miro) GTPase Gem1p, Mmr1p, and Ypt11p. A synthetic genetic array (SGA) screen revealed interactions between gem1Δ and deletions of genes that affect mitochondrial function or inheritance, including mmr1Δ. Synthetic sickness of gem1Δ mmr1Δ double mutants correlated with defective mitochondrial inheritance by large buds. Additional studies demonstrated that GEM1, MMR1, and YPT11 each contribute to mitochondrial inheritance. Mitochondrial accumulation in buds caused by overexpression of either Mmr1p or Ypt11p did not depend on Gem1p, indicating these three proteins function independently. Physical linkage of mitochondria with the endoplasmic reticulum (ER) has led to speculation that distribution of these two organelles is coordinated. We show that yeast mitochondrial inheritance is not required for inheritance or spreading of cortical ER in the bud. Moreover, Ypt11p overexpression, but not Mmr1p overexpression, caused ER accumulation in the bud, revealing a potential role for Ypt11p in ER distribution. This study demonstrates that multiple pathways influence mitochondrial inheritance in yeast and that Miro GTPases have conserved roles in mitochondrial distribution.

MITOCHONDRIA contribute to many cellular processes, including calcium homeostasis, cell death, cellular respiration, and metabolism. Studies in yeast, flies, worms, and mammals have established that mito-chondrial shape and distribution are important for organelle function and cell survival (recently reviewed by Karbowski and Youle 2003; Chan 2006; Frazier et al. 2006; Szabadkai et al. 2006). Moreover, mitochondrial function is particularly important in neurons, where synaptic mitochondria provide the necessary energy for neurotransmitter release and recycling (Hollenbeck 2005; Ly and Verstreken 2006; Rikhy et al. 2007). Studies in the budding yeast Saccharomyces cerevisiae have advanced understanding of processes that impinge on mitochon-drial function, including regulation of mitochondrial shape and distribution (recently reviewed by Shaw and Nunnari 2002; Okamoto and Shaw 2005; Escobar Henriques and Langer 2006; Griffin et al. 2006). Even in yeast, where mitochondrial respiration is dispensable, mitochondria are essential for cell survival (Altmann and Westermann 2005; Kispal et al. 2005). Mitochondria cannot be generated de novo and must arise from existing organelles in the mother cell. Therefore, transfer of mitochondria to the emerging daughter cell is an essential process (Mc C onnell et al. 1990; Warren and Wickner 1996).

Inheritance of the tubular mitochondrial network is actively regulated in dividing yeast cells. Mitochondria are inherited by small buds soon after bud emergence and initially appear to be associated with the bud tip. In addition, anchoring in the mother cell is thought to ensure that the mother retains a subset of mitochondria. By the time the mother and daughter are separated by cytokinesis, approximately equal amounts of mitochondria are distributed into each cell (Simon et al. 1997; Boldogh et al. 2001).

Although many aspects of mitochondrial distribution remain unclear, efficient mitochondrial distribution and inheritance in yeast requires the actin cytoskeleton. Monomeric actin polymerizes to form actin filaments, which are either bundled to make actin cables or clustered into actin cortical patches (Young et al. 2004). Cables are oriented along the mother-bud axis to facilitate bud-directed movement of cellular materials to the growing bud. Cortical actin patches, which typically function as sites of endocytosis (Kaksonen et al. 2003; Huckaba et al. 2004), localize to the new bud tip. As the bud enlarges and shifts to isotropic growth, cortical patches are distributed in the bud cortex (Pruyne and Bretscher 2000a,b;Moseley andGoode 2006). …

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