J. Biochem, 1998, Vol. 123, No. 1 128-135
© 1998 Japanese Biochemical Society
research-article |
Mechanism of Mitochondrial Import of Adenylate Kinase Isozymes1
,2,3,4
*Center for Gene Research, Yamaguchi University Ube, Yamaguchi 755
Department of Biochemistry, Yamaguchi University School of Medicine Ube, Yamaguchi 755
4To whom correspondence should be addressed. Tel: +81-836-22-2214, Fax: +81-836-22-2315, E-mail: F00623{at}sinet.ad.jp
Adenylate kinase (AK) is a ubiquitous enzyme that contributes to the homeostasis of the cellular adenine nucleotide composition. Three isozymes, AK1, AK2, and AK3, have so far been characterized in vertebrates. They are located in different tissues, while their primary and tertiary structures are similar. Among them, AK2 and AK3 are located in mitochondria, but unlike most mitochondrial proteins, both proteins lack a cleavable presequence. In this study, we first confirmed that AK2 is distributed in liver cells in both the cytosol and the intermembrane space of mitochondria, while AK3 is localized exclusively in the mitochondrial matrix. Next, we analyzed the process of import of AK2 and AK3 by incubating isolated rat mitochondria with proteins that were synthesized in a reticulocyte lysate translation system. The results indicated that both AK2 (an intermembrane-spacetargeting protein) and AK3 (a matrix-targeting protein) require an inner membrane electrochemical potential for their import. This finding for AK2 is in contrast with those of other noncleavable intermembrane-space-targeting proteins such as cytochrome c and cytochrome c heme lyase, which do not require the membrane potential for their import. In the transport process, AK2 and AK3 competed with the adrenodoxin precursor, which is imported into the matrix through a mechanism common to other mitochondrial matrix proteins. Thus, AK2 and AK3 were thought to be translocated into mitochondria through the same pathway as that for most mitochondrial protein precursors. Neither AK2, that was previously synthesized in reticulocyte lysates, nor AK2, that was purified from an Escherichia coli overexpression system, was imported into mitochondria in a post-translational import manner. In contrast, AK3 was imported into mitochondria after completion of protein synthesis. Thus, the import of AK2 is likely to be co-translational, and the co-translational import mechanism might contribute to the bi-topological distribution of AK2 in both the cytosol and mitochondria.
1This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.
2Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753
3Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194.
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