1. Overexpression of PEX14 results in mistargeting to mitochondria, accompanied by organelle fragmentation and clustering in human embryonic kidney cells.
- Author
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Jansen RLM, de Boer R, de Lange EMF, Koster J, Vlijm R, Waterham HR, and van der Klei IJ
- Subjects
- Humans, HEK293 Cells, Peroxins metabolism, Peroxins genetics, Protein Transport, Lipoproteins, Repressor Proteins, Mitochondria metabolism, Mitochondria genetics, Membrane Proteins metabolism, Membrane Proteins genetics, Peroxisomes metabolism, Peroxisomes genetics
- Abstract
Peroxisome biogenesis disorders are caused by pathogenic variants in genes involved in biogenesis and maintenance of peroxisomes. However, mitochondria are also often affected in these diseases. Peroxisomal membrane proteins, including PEX14, have been found to mislocalise to mitochondria in cells lacking peroxisomes. Recent studies indicated that this mislocalisation contributes to mitochondrial abnormalities in PEX3-deficient patient fibroblasts cells. Here, we studied whether mitochondrial morphology is also affected in PEX3-deficient HEK293 cells and whether PEX14 mislocalises to mitochondria in these cells. Using high-resolution imaging techniques, we show that although endogenous PEX14 mislocalises to mitochondria, mitochondrial morphology was normal in PEX3-KO HEK293 cells. However, we discovered that overexpression of tagged PEX14 in wild-type HEK293 cells resulted in its mitochondrial localisation, accompanied by altered mitochondrial morphology. Our data indicate that overexpression of tagged PEX14 alone directly or indirectly cause mitochondrial abnormalities in cells containing peroxisomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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