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

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.

Evolution of peroxisomes illustrates symbiogenesis

“…It was instrumental in showing that peroxisomes can be formed de novo from ER membranes [34,35,37]. However, the indications for a mitochondrial connection recently demonstrated in human fibroblasts by the group of McBride [11] have not been observed in yeast. How can this be?…”

“…These vesicles fuse with Pex16 containing ER-derived vesicles to give rise to de novo peroxisomes (as defined by import of peroxisomal proteins) [11]. In the "News & Views" accompanying the article, Hettema and Gould pinpoint differences between de novo peroxisome formation in mammalian cells and yeast [12].…”

Mitochatting – If only we could be a fly on the cell wall

“…The extent of interaction is so high that it was suggested that peroxisomes have a mitochondrial origin and that they emerged as functionally specialized mitochondria [100]. Indeed, new evidence now demonstrates that pre-peroxisomal vesicles bud from mitochondria [101].…”

Peroxisome Function, Biogenesis, and Dynamics in Plants

“…Moreover, mammalian PEX3 can be inserted into the mitochondrial outer membrane, and mitochondrion-derived preperoxisomal vesicles can fuse with PEX19-containing ERderived preperoxisomal vesicles to form import-competent peroxisomes (Sugiura et al, 2017).…”