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bioRxiv · 10.1101/2022.04.22.489171

Peroxisomal ATPase ATAD1 acts in quality control of the protein import machinery

Ott, J.·Sehr, J.·Lindemann, C.·Barkovits, K.·Bader, V.·Winklhofer, K.·Marcus, K.·Schliebs, W.·Erdmann, R.
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Abstract

ATAD1 is an AAA-ATPase which shows a dual localization at mitochondria and peroxisomes. While its peroxisomal function is not known, in mitochondria ATAD1 is part of a quality control mechanism extracting mislocalised tail-anchored and accumulated precursor proteins from the outer membrane. Here, we studied the peroxisomal interactome of ATAD1 and could show that human ATAD1 interacts with PEX5, a cytosolic receptor for peroxisomal matrix proteins which transiently inserts into peroxisomal membranes. Upon cargo-release, mono-ubiquitinated PEX5 is recycled into the cytosol by the AAA-peroxins PEX1 and PEX6. The accumulation of ubiquitinated PEX5 is known to trigger degradation of whole organelles called pexophagy. Here, we used ATAD1-, PEX1- and ATAD1/PEX1-CRISPR-Knockout cell lines to investigate the physiological role of an ATAD1-PEX5 interaction. We could show an influence of ATAD1 on the stability of accumulated PEX5 and hypothesize a role in a peroxisomal quality control mechanism enabling clearance of ubiquitinated receptor from the membrane.

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Ott, J., Sehr, J., Lindemann, C., Barkovits, K., Bader, V., Winklhofer, K., Marcus, K., Schliebs, W., Erdmann, R.. 2022-04-22. Peroxisomal ATPase ATAD1 acts in quality control of the protein import machinery. https://doi.org/10.1101/2022.04.22.489171

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