A hypomorphic allele of the first N-glycosylation gene, ALG7, causes mitochondrial defects in yeast

被引:21
作者
Mendelsohn, RD
Helmerhorst, EJ
Cipollo, JF
Kukuruzinska, MA [1 ]
机构
[1] Boston Univ, Ctr Med, Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02215 USA
[2] Boston Univ, Sch Med, Dept Biochem, Ctr Med, Boston, MA USA
[3] Boston Univ, Ctr Med, Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2005年 / 1723卷 / 1-3期
关键词
N-glycosylation; ALG7; hypomorph; mitochondrial gene; respiration; Saccharomyces cerevisiae;
D O I
10.1016/j.bbagen.2005.01.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The modification of proteins at asparagine residues with oligosaccharides (N-glycans) plays critical roles in diverse cell functions. N-glycans originate from a common lipid-linked oligosaccharide (LLO) precursor whose synthesis is initiated by the Dol-P-dependent GlcNAc-1-P transferase (GPT) encoded by an essential ALG7 gene. To identify cellular processes affected by ALG7 and N-glycosylation, we replaced the genomic copy of ALG7 with its hypomorphic allele in two genetically distinct haploid yeast cells. We show that ALG7 knockdown gave rise to an unexpected phenotype of mitochondrial dysfunction. The alg7 mutants did not grow on glycerol and DNA arrays revealed the absence of mitochondrial genes' expression. Accordingly, the alg7 mutants displayed no detectable mtDNA and respiratory activity. Both mutants exhibited diminished abundance of LLO and under-glycosylation of carboxypeptidase Y (CPY). Moreover, another N-glycosylation mutant with a LLO defect, alg6, was respiratory deficient. Collectively, our studies provide evidence that the dysregulation of N-glycosylation in haploid yeast cells leads to mitochondrial dysfunction. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:33 / 44
页数:12
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