Multiple variants of the human presequence translocase motor subunit Magmas govern the mitochondrial import.

Mitochondrial protein translocation is an intricately regulated process that requires dedicated translocases at the outer and inner membranes. The presequence translocase complex, translocase of the inner membrane 23, facilitates most of the import of preproteins containing presequences into the mitochondria, and its primary structural organization is highly conserved. As part of the translocase motor, two J-proteins, DnaJC15 and DnaJC19, are recruited to form two independent translocation machineries (translocase A and translocase B, respectively). On the other hand, the J-like protein subunit of translocase of the inner membrane 23, Mitochondria-associated granulocyte-macrophage colony-stimulating factor signaling molecule (Magmas) (orthologous to the yeast subunit Pam16), can regulate human import-motor activity by forming a heterodimer with DnaJC19 and DnaJC15. However, the precise coordinated regulation of two human import motors by a single Magmas protein is poorly understood. Here, we report two additional Magmas variants (Magmas-1 and Magmas-2) constitutively expressed in the mammalian system. Both the Magmas variants are functional orthologs of Pam16 with an evolutionarily conserved J-like domain critical for cell survival. Moreover, the Magmas variants are peripherally associated with the inner membrane as part of the human import motor for translocation. Our results demonstrate that Magmas-1 is predominantly recruited to translocase B, whereas Magmas-2 is majorly associated with translocase A. Strikingly, both the variants exhibit differential J-protein inhibitory activity in modulating import motor, thereby regulating overall translocase function. Based on our findings, we hypothesize that additional Magmas variants are of evolutionary significance in humans to maximize protein import in familial-linked pathological conditions. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Tejashree Pradip Waingankar, Patrick D'Silva. Multiple variants of the human presequence translocase motor subunit Magmas govern the mitochondrial import. The Journal of biological chemistry. 2021 Dec;297(6):101349

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PMID: 34715125

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