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Department of Cell Biology and Anatomy, The Johns Hopkins
University School of Medicine, Baltimore, Maryland 21205
The Tim23 protein is an essential inner membrane (IM) component of
the yeast mitochondrial protein import pathway. Tim23p does not carry
an amino-terminal presequence; therefore, the targeting information
resides within the mature protein. Tim23p is anchored in the IM via
four transmembrane segments and has two positively charged loops facing
the matrix. To identify the import signal for Tim23p, we have
constructed several altered versions of the Tim23 protein and examined
their function and import in yeast cells, as well as their import into
isolated mitochondria. We replaced the positively charged amino acids
in one or both loops with alanine residues and found that the positive
charges are not required for import into mitochondria, but at least one
positively charged loop is required for insertion into the IM.
Furthermore, we find that the signal to target Tim23p to mitochondria
is carried in at least two of the hydrophobic transmembrane segments.
Our results suggest that Tim23p contains separate import signals: hydrophobic segments for targeting Tim23p to mitochondria, and positively charged loops for insertion into the IM. We therefore propose that Tim23p is imported into mitochondria in at least two
distinct steps.
Corresponding author.
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