Peroxisomes control mitochondrial dynamics and the mitochondrion-dependent apoptosis pathway

• Published in: Journal of cell science Vol. 132; no. 11
• Main Authors: Tanaka, Hideaki, Okazaki, Tomohiko, Aoyama, Saeko, Yokota, Mutsumi, Koike, Masato, Okada, Yasushi, Fujiki, Yukio, Gotoh, Yukiko
• Format: Journal Article
• Language: English
• Published: England 31.05.2019
• Subjects: Caspase; Organelle; Peroxisome; Mitochondria; Apoptosis; Drp1
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.224766

Peroxisomes cooperate with mitochondria in the performance of cellular metabolic functions, such as fatty acid oxidation and the maintenance of redox homeostasis. However, whether peroxisomes also regulate mitochondrial fission-fusion dynamics or mitochondrion-dependent apoptosis remained unclear. We now show that genetic ablation of the peroxins Pex3 or Pex5, which are essential for peroxisome biogenesis, results in mitochondrial fragmentation in mouse embryonic fibroblasts (MEFs) in a manner dependent on Drp1 (also known as DNM1L). Conversely, treatment with 4-PBA, which results in peroxisome proliferation, resulted in mitochondrial elongation in wild-type MEFs, but not in Pex3-knockout MEFs. We further found that peroxisome deficiency increased the levels of cytosolic cytochrome and caspase activity under basal conditions without inducing apoptosis. It also greatly enhanced etoposide-induced caspase activation and apoptosis, which is indicative of an enhanced cellular sensitivity to death signals. Taken together, our data unveil a previously unrecognized role for peroxisomes in the regulation of mitochondrial dynamics and mitochondrion-dependent apoptosis. Effects of peroxin gene mutations on mitochondrion-dependent apoptosis may contribute to pathogenesis of peroxisome biogenesis disorders.This article has an associated First Person interview with the first author of the paper.