Active Segregation of Yeast Mitochondria by Myo2 Is Essential and Mediated by Mmr1 and Ypt11

•Active mitochondrial segregation is an essential process independent of ER segregation•Mitochondrial segregation is an essential specific function of myosin V, Myo2•Active segregation depends on association of Ypt11 or Mmr1 with Myo2•Without mitochondrial segregation, cells continue to divide, giving rise to dead cells

SummaryActive segregation of essential organelles is required for successful cell division. The essential budding yeast myosin V Myo2 actively segregates most organelles along polarized actin cables [1 and 2]. The mechanism of mitochondrial segregation remains controversial, with movement driven by actin polymerization [3, 4 and 5], movement driven by association with transported cortical endoplasmic reticulum (ER) [6 and 7], and direct transport by Myo2 [8, 9, 10 and 11] proposed as models. Two nonessential proteins, Mmr1 and the Rab GTPase Ypt11, bind Myo2 and have been implicated in mitochondrial inheritance, although their specific roles are also contended [7, 8, 9 and 11]. We generated myo2sens mutations that exhibit no overt phenotype but render MMR1 essential and have compromised Ypt11 binding. We then isolated myo2sensmmr1ts conditional mutants and determined that they have a specific and severe defect in active mitochondrial inheritance, revealing mitochondrial transport by Myo2 as an essential function. ypt11Δ mmr1ts cells also have conditional defects in growth and active transport of mitochondria into the bud, both of which are suppressed by artificially forcing mitochondrial inheritance. At the restrictive temperature, cells defective in mitochondrial inheritance give rise to dead buds that go through cytokinesis normally, showing no evidence of a proposed cell-cycle mitochondrial inheritance checkpoint [12]. Thus, active mitochondrial inheritance is an essential process and a function of Myo2 that requires either Mmr1 or Ypt11.