Mitochondrial PEX14 supports peroxisome biogenesis
- 1Bielefeld University
Abstract
Peroxisomes are essential for cellular homeostasis and human health due to their central metabolic and physiological functions. The peroxisomal membrane protein PEX14 is indispensable for matrix protein import into peroxisomes. Recent studies support a hybrid model in which pre-peroxisomal vesicles originating from both, mitochondria and the endoplasmic reticulum, fuse to generate peroxisomes. PEX14 has repeatedly been observed at mitochondria in biogenesis disease models or upon protein overexpression, but such localization has generally been interpreted as aberrant mislocalization. Whether endogenous PEX14 naturally localizes to mitochondria and contributes to peroxisome biogenesis has remained unknown. Here, using high-content and super-resolution microscopy, we demonstrate that endogenous PEX14 localizes to the mitochondrial outer membrane. We show that ectopically expressed PEX14 accumulates at mitochondria, and PEX14 variants unable to access mitochondria and restricted to peroxisomes fail to rescue the PEX14 knockout phenotype. Vice versa, a mitochondria-targeted PEX14 variant supports peroxisome biogenesis. Our results identify the physiological mitochondrial pool of PEX14 in human cells and establish it as an essential intermediate in de novo peroxisome biogenesis.
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BibTeX
@misc{nemeita2026mitochondrial,
title = {{Mitochondrial PEX14 supports peroxisome biogenesis}},
author = {B. Nemeita and A. Hammann and S. Karki and T. Soykan and L. Wieland and M. Lehmann and S. Thoms},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.759530},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.759530v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Mitochondrial PEX14 supports peroxisome biogenesis
AU - B. Nemeita
AU - A. Hammann
AU - S. Karki
AU - T. Soykan
AU - L. Wieland
AU - M. Lehmann
AU - S. Thoms
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.759530
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.759530v1
AB - Peroxisomes are essential for cellular homeostasis and human health due to their central metabolic and physiological functions. The peroxisomal membrane protein PEX14 is indispensable for matrix protein import into peroxisomes. Recent studies support a hybrid model in which pre-peroxisomal vesicles originating from both, mitochondria and the endoplasmic reticulum, fuse to generate peroxisomes. PEX14 has repeatedly been observed at mitochondria in biogenesis disease models or upon protein overexpression, but such localization has generally been interpreted as aberrant mislocalization. Whether endogenous PEX14 naturally localizes to mitochondria and contributes to peroxisome biogenesis has remained unknown. Here, using high-content and super-resolution microscopy, we demonstrate that endogenous PEX14 localizes to the mitochondrial outer membrane. We show that ectopically expressed PEX14 accumulates at mitochondria, and PEX14 variants unable to access mitochondria and restricted to peroxisomes fail to rescue the PEX14 knockout phenotype. Vice versa, a mitochondria-targeted PEX14 variant supports peroxisome biogenesis. Our results identify the physiological mitochondrial pool of PEX14 in human cells and establish it as an essential intermediate in de novo peroxisome biogenesis.
ER -