The Tim54p-Tim22p Complex Mediates Insertion of Proteins into the Mitochondrial Inner Membrane

doi:10.1083/jcb.139.7.1663

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© The Rockefeller University Press, 0021-9525/1997//1663 $5.00
The Journal of Cell Biology, Volume 139, Number 7, , 1997 1663-1675

Article

The Tim54p–Tim22p Complex Mediates Insertion of Proteins into the Mitochondrial Inner Membrane

Oliver Kerscher, Jason Holder, Maithreyan Srinivasan, Roxanne S. Leung, and Robert E. Jensen

Department of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

We have identified a new protein, Tim54p, located in the yeastmitochondrial inner membrane. Tim54p is an essential importcomponent, required for the insertion of at least two polytopicproteins into the inner membrane, but not for the translocationof precursors into the matrix. Several observations suggest that Tim54p and Tim22p are part of a protein complex in theinner membrane distinct from the previously characterized Tim23p-Tim17pcomplex. First, multiple copies of the TIM22 gene, but notTIM23 or TIM17, suppress the growth defect of a tim54-1 temperature-sensitivemutant. Second, Tim22p can be coprecipitated with Tim54p fromdetergent-solubilized mitochondria, but Tim54p and Tim22p donot interact with either Tim23p or Tim17p. Finally, the tim54-1mutation destabilizes the Tim22 protein, but not Tim23p or Tim17p. Our results support the idea that the mitochondrial inner membranecarries two independent import complexes: one required for thetranslocation of proteins across the inner membrane (Tim23p–Tim17p),and the other required for the insertion of proteins into theinner membrane (Tim54p–Tim22p).

Abbreviations used in this paper: CEN, centome-containing plasmid; DIC, differential interference contrast; HA, hemagglutinin; IM, inner membrane; Tim, translocase inner membrane; Tom, translocase outer membrane.

Address all correspondence to Robert E. Jensen, Department ofCell Biology and Anatomy, The Johns Hopkins University Schoolof Medicine, 725 N. Wolfe St., Baltimore, MD 21205. Tel.: (410)955-7291; Fax: (410) 955-4129; E-mail: rob_jensen{at}qmail.bs.jhu.edu

O. Kerscher and J. Holder contributed equally to this work.

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