High impact information on YME1

• Here we investigate the AAA domain of the yeast protein Yme1, a subunit of the iota-AAA protease located in the inner membrane of mitochondria [1].
• Treatment of cells with cycloheximide caused a similar imbalance in the accumulation of COX subunits, and enhanced mRNA for Lon and Yme1, the latter another mitochondrial ATP-dependent protease [2].
• Furthermore, Yme1 has a new function in protein translocation, indicating that the intermembrane space harbors diverse pathways for protein translocation [3].
• The yme1 cold-sensitive growth phenotype is suppressed by yme2 mutations [4].
• We also cloned the OSD1 gene by complementation of the temperature sensitivity of osd1-1 mutants with a COXIV+ genetic background on a nonfermentable glycerol medium [5].

Biological context of YME1

• The cloned YME1 gene complements all of these phenotypes [6].
• The protein encoded by YME1, Yme1p, contains two highly conserved sequence elements, one implicated in the binding and hydrolysis of ATP, and the second characteristic of active site residues found in neutral, zinc-dependent proteases [7].
• Deletion of YME1, coding for the i-AAA protease in the inner membrane, abolished peptide generation in the intermembrane space and led to the induction of nuclear genes with functions in mitochondrial gene expression and the biogenesis of the respiratory chain [8].
• In yeast, three AAA superfamily metalloproteases (Yme1p, Afg3p and Rca1p) are localized to the mitochondrial inner membrane where they perform roles in the assembly and turnover of the respiratory chain complexes [9].
• We have investigated the function of the proposed human orthologue of yeast Yme1p, encoded by the YME1L gene on chromosome 10p [9].

Anatomical context of YME1

• The gene product, Yme1p, is immunologically detectable as an 82-kDa protein present in mitochondria [6].
• These findings suggest that yme1, yme2, yme4 and yme6 mutations alter mitochondrial functions and thereby lead to an increased rate of DNA escape from the organelle [10].
• The evidence presented here suggests that the abnormal mitochondria of a yme1 strain are degraded by the vacuole [11].
• The data support a model in which Yme1p is an ATP and zinc-dependent protease associated with the matrix side of the inner mitochondrial membrane [7].

Associations of YME1 with chemical compounds

• In addition to increasing the rate of mtDNA escape, yme1 mutations also caused a heat-sensitive respiratory deficient phenotype at 37 degrees and a cold-sensitive growth defect on complete glucose medium at 14 degrees [10].
• Benzoate utilization by S. cerevisiae expressing ZbYME2 requires a functional mitochondrial respiratory chain, but not the native Yme1p and Yme2p of the mitochondrion [12].
• Mitochondria isolated from yme1 yeast generated a membrane potential upon the addition of succinate, but unlike mitochondria isolated either from wild-type yeast or from yeast bearing yme1 and a suppressing mutation, were unable to generate a membrane potential upon the addition of ATP [13].

Regulatory relationships of YME1

• The synthetic respiratory growth defect of yme1 yme2 yeast strains is suppressed by recessive mutations in YNT20 [14].

Other interactions of YME1

• Neither Afg3p nor Yme1p is responsible for the degradation of Cox subunits [15].
• Absence of the mitochondrial AAA protease Yme1p restores F0-ATPase subunit accumulation in an oxa1 deletion mutant of Saccharomyces cerevisiae [15].
• All 21 mutations were recessive and fell into six complementation groups, termed YME1-YME6 [10].
• Most importantly, ADD appeared to be specifically suppressed to various extents by deletions of any of the YME1, AFG3, or RCA1 genes encoding membrane-associated mitochondrial proteases, probably because the amphipathic structures caused a stronger association with the mitochondrial inner membrane and its associated proteases [16].
• For instance, we found an inverted expression profile relationship between genes YME1 and YNT20, where the latter has been experimentally documented as a bypass suppressor of the former [17].

Analytical, diagnostic and therapeutic context of YME1

• First, electron microscopy of Yme1p-deficient strains revealed mitochondria physically associated with the vacuole via electron dense structures [11].

References