Pam18

Pam18 is a small mitochondrial inner-membrane J-domain protein that functions as a co-chaperone for mitochondrial Hsp70 in the TIM23 translocase motor. In the yeast import machinery, Pam18 forms a functional unit with Pam16, and together with Tim44, they associate with the TIM23 complex to drive protein translocation across the inner membrane. The J-domain of Pam18 in the matrix activates the ATPase activity of mtHsp70 (Ssc1), coupling ATP hydrolysis to polypeptide movement into the mitochondrial matrix.

Structurally, Pam18 contains a single transmembrane segment that anchors it in the inner membrane, with the J-domain oriented toward the matrix. The J-domain contains the conserved HPD motif, essential for stimulating mtHsp70’s ATPase activity. Activity is regulated by its interaction with Pam16, a non-J-domain partner that modulates the stimulatory effect of Pam18 on mtHsp70 to ensure proper motor function.

Functionally, the Pam16–Pam18 complex enhances the energy-dependent translocation of precursor proteins through the TIM23 channel, supporting import into the matrix and, in some cases, integration into the inner membrane. This motor contributes to the efficiency and accuracy of mitochondrial protein import for a wide range of nucleus-encoded proteins bearing N-terminal targeting signals.

Genetically, PAM18 is important for mitochondrial function in yeast; loss or disruption of PAM18 leads to import defects and impaired respiration. Homologs of Pam18 exist in a broad range of eukaryotes, reflecting a conserved role for J-domain co-chaperones in mitochondrial protein import.