Lon/Pim1-mediated degradation of presequence translocase-associated motor components Pam16 and Pam18 in <i>Saccharomyces cerevisiae</i>

Mitochondrial protein homeostasis depends mainly on the efficient import and folding of nuclear-encoded proteins, and defects in this process can lead to proteotoxicity, which is harmful to the cell. Mitochondrial chaperones and proteases are essential defense mechanisms that ensure dysfunctional proteins' proper concentration, folding, and degradation. Lon protease 1 (Pim1 in yeast) is the mitochondrial matrix protease known to prevent protein aggregation by degrading unfolded proteins. Here, we show that two essential components of ATP-dependent presequence translocase and associated motor (PAM complex), Pam18 and Pam16, are specifically targeted for degradation by the proteolytically active Lon/Pim1, both in vitro and in vivo. Furthermore, overexpression of Pam18 and Pam16 exacerbates the growth defect of the delta pim1 strain. Hence, our study reveals, for the first time, that components involved in protein import are substrates of Pim1, which could have potential implications for regulating mitochondrial protein import and proteostasis.