Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes.

TitleNewly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes.
Publication TypeJournal Article
Year of Publication2017
AuthorsSugiura, A, Mattie, S, Prudent, J, McBride, HM
JournalNature
Volume542
Issue7640
Pagination251-254
Date Published2017 02 09
ISSN1476-4687
KeywordsBacterial Proteins, Cell Line, Endoplasmic Reticulum, Fibroblasts, Humans, Intracellular Membranes, Lipoproteins, Luminescent Proteins, Membrane Proteins, Mitochondria, Organelle Biogenesis, Peroxisomes, Protein Transport, Repressor Proteins, Zellweger Syndrome
Abstract

Peroxisomes function together with mitochondria in a number of essential biochemical pathways, from bile acid synthesis to fatty acid oxidation. Peroxisomes grow and divide from pre-existing organelles, but can also emerge de novo in the cell. The physiological regulation of de novo peroxisome biogenesis remains unclear, and it is thought that peroxisomes emerge from the endoplasmic reticulum in both mammalian and yeast cells. However, in contrast to the yeast system, a number of integral peroxisomal membrane proteins are imported into mitochondria in mammalian cells in the absence of peroxisomes, including Pex3, Pex12, Pex13, Pex14, Pex26, PMP34 and ALDP. Overall, the mitochondrial localization of peroxisomal membrane proteins in mammalian cells has largely been considered a mis-targeting artefact in which de novo biogenesis occurs exclusively from endoplasmic reticulum-targeted peroxins. Here, in following the generation of new peroxisomes within human patient fibroblasts lacking peroxisomes, we show that the essential import receptors Pex3 and Pex14 target mitochondria, where they are selectively released into vesicular pre-peroxisomal structures. Maturation of pre-peroxisomes containing Pex3 and Pex14 requires fusion with endoplasmic reticulum-derived vesicles carrying Pex16, thereby providing full import competence. These findings demonstrate the hybrid nature of newly born peroxisomes, expanding their functional links to mitochondria.

DOI10.1038/nature21375
Alternate JournalNature
Citation Key10.1038/nature21375
PubMed ID28146471