Dynamin-like Protein 1 Is Involved in Peroxisomal Fission

Abstract

The mammalian dynamin-like protein 1 (DLP1), a member of the dynamin family of large GTPases, possesses mechanochemical properties known to constrict and tubulate membranes. In this study, we have combined two experimental approaches, induction of peroxisome proliferation by Pex11p␤ and expression of dominant-negative mutants, to test whether DLP1 plays a role in peroxisomal growth and division. We were able to localize DLP1 in spots on tubular peroxisomes in HepG2 cells. In addition, immunoblot analysis revealed the presence of DLP1 in highly purified peroxisomal fractions from rat liver and an increase of DLP1 after treatment of rats with the peroxisome proliferator bezafibrate. Expression of a dominant negative DLP1 mutant deficient in GTP hydrolysis (K38A) either alone or in combination with Pex11p␤ caused the appearance of tubular peroxisomes but had no influence on their intracellular distribution. In co-expressing cells, the formation of tubulo-reticular networks of peroxisomes was promoted, and peroxisomal division was completely inhibited. These findings were confirmed by silencing of DLP1 using siRNA. We propose a direct role for the dynamin-like protein DLP1 in peroxisomal fission and in the maintenance of peroxisomal morphology in mammalian cells.

Peroxisome proliferator-activated receptor α-independent peroxisome proliferation

“…DLP1 expression is increased in rat livers treated with bezafibrate [20], a potent PPARδ agonist and a moderate PPARα agonist [24]. However, it remains unclear whether DLP1 contributes to peroxisome proliferation in either genotype through PPARδ activation, because fenofibrate is PPARα agonist and is not known to activate PPARδ.…”

“…4B). Next, we examined the mRNA level of DLP1, a mammalian dynamin-related protein required for peroxisome division [18,20]. The DLP1 mRNA level was increased approximately 2.5-fold in the fenofibrate-treated wild-type mice (Fig.…”

hFis1, a Novel Component of the Mammalian Mitochondrial Fission Machinery

“…Expression of DRP1 in C. elegans promotes mitochondrial fission, but expression of mammalian Drp1 has no effect on the morphology of mitochondria. In addition Drp1 has recently been implicated in the division of peroxisomes (11). Furthermore, the regulation of mitochondrial morphology is a key factor in the process of apoptosis.…”

Light Induces Peroxisome Proliferation in Arabidopsis Seedlings through the Photoreceptor Phytochrome A, the Transcription Factor HY5 HOMOLOG, and the Peroxisomal Protein PEROXIN11b

“…The five Arabidopsis PEX11 isoforms, PEX11a to PEX11e, were shown to promote peroxisome elongation and population increase with some level of specificity and redundancy (Lingard and Trelease, 2006;Orth et al, 2007). In addition to PEX proteins, the large GTPase dynaminrelated protein (DRP) and FISSION1 (FIS1) proteins in yeast and mammals function in the late stages of peroxisome division, whereby the integral membrane protein FIS1 recruits the mechanochemical enzyme DRP to execute the tubulation and separation of peroxisomal membranes (Koch et al, 2003(Koch et al, , 2005Kobayashi et al, 2007). Interestingly, at least in yeast and mammals, the division machinery of peroxisomes and mitochondria seems to share the same DRP and FIS1 orthologs (Koch et al, 2005;Thoms and Erdmann, 2005;Schrader and Yoon, 2007).…”