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Published online
doi:10.1083/jcb.200812018
The Journal of Cell Biology, Vol. 185, No. 6, 1029-1045
The Rockefeller University Press, 0021-9525 $30.00
© Tamura et al.
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Article

Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria



Yasushi Tamura1, Toshiya Endo2, Miho Iijima1, and Hiromi Sesaki1

1 Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205
2 Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya 464-8602, Japan

Correspondence to Hiromi Sesaki: hsesaki{at}jhmi.edu

Cardiolipin, a unique phospholipid composed of four fatty acid chains, is located mainly in the mitochondrial inner membrane (IM). Cardiolipin is required for the integrity of several protein complexes in the IM, including the TIM23 translocase, a dynamic complex which mediates protein import into the mitochondria through interactions with the import motor presequence translocase–associated motor (PAM). In this study, we report that two homologous intermembrane space proteins, Ups1p and Ups2p, control cardiolipin metabolism and affect the assembly state of TIM23 and its association with PAM in an opposing manner. In ups1{Delta} mitochondria, cardiolipin levels were decreased, and the TIM23 translocase showed altered conformation and decreased association with PAM, leading to defects in mitochondrial protein import. Strikingly, loss of Ups2p restored normal cardiolipin levels and rescued TIM23 defects in ups1{Delta} mitochondria. Furthermore, we observed synthetic growth defects in ups mutants in combination with loss of Pam17p, which controls the integrity of PAM. Our findings provide a novel molecular mechanism for the regulation of cardiolipin metabolism.

Abbreviations used in this paper: AAC, ATP/ADP carrier; BN, blue native; DHFR, dihydrofolate reductase; IM, inner membrane; IMS, intermembrane space; OM, outer membrane; PAM, presequence translocase–associated motor; PE, phosphatidylethanolamine; PiC, phosphate carrier; PRELI, protein of relevant evolutionary lymphoid interest; PS, phosphatidylserine; TOM, translocase of the OM.

© 2009 Tamura et al.
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