The presequence translocase-associated protein import motor of mitochondria. Pam16 functions in an antagonistic manner to Pam18

J Biol Chem. 2004 Sep 3;279(36):38047-54. doi: 10.1074/jbc.M404319200. Epub 2004 Jun 24.


Transport of preproteins into the mitochondrial matrix requires the presequence translocase of the inner membrane (TIM23 complex) and the presequence translocase-associated motor (PAM). The motor consists of five essential subunits, the mitochondrial heat shock protein 70 (mtHsp70) and four cochaperones, the nucleotide exchange-factor Mge1, the translocase-associated fulcrum Tim44, the J-protein Pam18, and Pam16. Pam16 forms a complex with Pam18 and displays similarity to J-proteins but lacks the canonical tripeptide motif His-Pro-Asp (HPD). We report that Pam16 does not function as a typical J-domain protein but, rather, antagonizes the function of Pam18. Pam16 specifically inhibits the Pam18-mediated stimulation of the ATPase activity of mtHsp70. The inclusion of the HPD motif in Pam16 does not confer the ability to stimulate mtHsp70 activity. Pam16-HPD fully substitutes for wild-type Pam16 in vitro and in vivo but is not able to replace Pam18. Pam16 represents a new type of cochaperone that controls the stimulatory effect of the J-protein Pam18 and regulates the interaction of mtHsp70 with precursor proteins during import into mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Membrane Transport Modulators
  • Membrane Transport Proteins / antagonists & inhibitors
  • Membrane Transport Proteins / metabolism*
  • Mitochondrial Membrane Transport Proteins
  • Molecular Sequence Data
  • Saccharomyces cerevisiae Proteins / antagonists & inhibitors
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Membrane Transport Modulators
  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • PAM18 J protein, S cerevisiae
  • Pam16 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins