Tom20-mediated mitochondrial protein import in muscle cells during differentiation

被引:44
作者
Grey, JY
Connor, MK
Gordon, JW
Yano, M
Mori, M
Hood, DA
机构
[1] York Univ, Dept Biol, Toronto, ON M3J 1P3, Canada
[2] York Univ, Dept Kinesiol & Hlth Sci, Toronto, ON M3J 1P3, Canada
[3] Kumamoto Univ, Sch Med, Dept Mol Genet, Kumamoto 862, Japan
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2000年 / 279卷 / 05期
关键词
mitochondrial biogenesis; antisense oligodeoxynucleotides; thyroid hormone; translocases of the outer membrane;
D O I
10.1152/ajpcell.2000.279.5.C1393
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mitochondrial biogenesis is accompanied by an increased expression of components of the protein import machinery, as well as increased import of proteins destined for the matrix. We evaluated the role of the outer membrane receptor Tom20 by varying its expression and measuring changes in the import of malate dehydrogenase (MDH) in differentiating C2C12 muscle cells. Cells transfected with Tom20 had levels that were twofold higher than in control cells. Labeling of cells followed by immunoprecipitation of MDH revealed equivalent increases in MDH import. This parallelism between import rate and Tom20 levels was also evident as a result of thyroid hormone treatment. Using antisense oligodeoxynucleotides, we inhibited Tom20 expression by 40%, resulting in 40-60% reductions in MDH import. In vitro assays also revealed that import into the matrix was more sensitive to Tom20 inhibition than import into the outer membrane. These data indicate a close relationship between induced changes in Tom20 and the import of a matrix protein, suggesting that Tom20 is involved in determining the kinetics of import. However, this relationship was dissociated during normal differentiation, since the expression of Tom20 remained relatively constant, whereas imported MDH increased 12-fold. Thus Tom20 is important in determining import during organelle biogenesis, but other mechanisms (e.g., intramitochondrial protein degradation or nuclear transcription) likely also play a role in establishing the final mitochondrial phenotype during normal muscle differentiation.
引用
收藏
页码:C1393 / C1400
页数:8
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