Inactivation of Yme1p, a mitochondrially-localized ATP-dependent metallo-protease in the yeast Saccharomyces cerevisiae, causes a high rate of DNA escape from mitochondria to the nucleus as well as pleiotropic functional and morphological mitochondrial defects. The evidence presented here suggests that the abnormal mitochondria of a yme1 strain are degraded by the vacuole. First, electron microscopy of Yme1p-deficient strains revealed mitochondria physically associated with the vacuole via electron dense structures. Second, disruption of vacuolar function affected the frequency of mitochondrial DNA escape from yme1 and wild-type strains. Both PEP4 or PRC1 gene disruptions resulted in a lower frequency of mitochondrial DNA escape. Third, an in vivo assay that monitors vacuole-dependent turnover of the mitochondrial compartment demonstrated an increased rate of mitochondrial turnover in yme1 yeast when compared to the rate found in wild-type yeast. In this assay, vacuolar alkaline phosphatase, encoded by PHO8, was targeted to mitochondria in a strain bearing disruption to the genomic PHO8 locus. Maturation of the mitochondrially localized alkaline phosphatase pro-enzyme requires proteinase A, which is localized in the vacuole. Therefore, alkaline phosphatase activity reflects vacuole-dependent turnover of mitochondria. This assay reveals that mitochondria of a yme1 strain are taken up by the vacuole more frequently than mitochondria of an isogenic wild-type strain when these yeast are cultured in medium necessitating respiratory growth. Degradation of abnormal mitochondria is one pathway by which mitochondrial DNA escapes and migrates to the nucleus.
Escape of mitochondrial DNA to the nucleus in yme1 yeast is mediated by vacuolar-dependent turnover of abnormal mitochondrial compartments
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C.L. Campbell, P.E. Thorsness; Escape of mitochondrial DNA to the nucleus in yme1 yeast is mediated by vacuolar-dependent turnover of abnormal mitochondrial compartments. J Cell Sci 15 August 1998; 111 (16): 2455–2464. doi: https://doi.org/10.1242/jcs.111.16.2455
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