ATAD1 prevents clogging of TOM and damage caused by un-imported mitochondrial proteins.

Mitochondria require the constant import of nuclear-encoded proteins for proper functioning. Impaired protein import not only depletes mitochondria of essential factors but also leads to toxic accumulation of un-imported proteins outside the organelle. Here, we investigate the consequences of impaired mitochondrial protein import in human cells. We demonstrate that un-imported proteins can clog the mitochondrial translocase of the outer membrane (TOM). ATAD1, a mitochondrial ATPase, removes clogged proteins from TOM to clear the entry gate into the mitochondria. ATAD1 interacts with both TOM and stalled proteins, and its knockout results in extensive accumulation of mitochondrial precursors as well as decreased protein import. Increased ATAD1 expression contributes to improved fitness of cells with inefficient mitochondrial protein import. Overall, we demonstrate the importance of the ATAD1 quality control pathway in surveilling protein import and its contribution to cellular health. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

John Kim, Madeleine Goldstein, Lauren Zecchel, Ryan Ghorayeb, Christopher A Maxwell, Hilla Weidberg. ATAD1 prevents clogging of TOM and damage caused by un-imported mitochondrial proteins. Cell reports. 2024 Aug 27;43(8):114473

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PMID: 39024102

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