The Dynamin-like GTPase DLP1 Is Essential for Peroxisome Division and Is Recruited to Peroxisomes in Part by PEX11

Abstract

Peroxisome division involves the conserved PEX11 peroxisomal membrane proteins and in yeast has been shown to require Vps1p, a dynamin-like protein. We show here that DLP1, the human homolog of the yeast DNM1 and VPS1 genes, plays an important role in peroxisome division in human cells. Disruption of DLP1 function by either RNA interference or overexpressing dominant negative DLP1 mutants causes a dramatic reduction in peroxisome abundance, although overexpression of functional DLP1 has no effect on peroxisome abundance. Overexpression of PEX11 induces peroxisome division in a multistep process involving elongation of preexisting peroxisomes followed by their division. We find that DLP1 is dispensable for the first phase of this process but essential for the second. Furthermore, we show that DLP1 associates with peroxisomes and that PEX11 overexpression recruits DLP1 to peroxisome membranes. However, we were unable to detect physical interaction between PEX11 and DLP1, and the stoichiometry of PEX11 and peroxisome-associated DLP1 was far less than 1:1. Based on these and other aspects, we propose that DLP1 performs an essential but transient role in peroxisome division and that PEX11 promotes peroxisome division by recruiting DLP1 to peroxisome membranes through an indirect mechanism.

Charcot‐Marie‐Tooth disease‐associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission

“…Reduced levels of GDAP1 led to elongated peroxisomes. This effect was even more pronounced after knockdown of Drp1, where most peroxisomes were tubular as described (Fig 2A) [6,8]. This experiment demonstrated that loss of GDAP1 alters peroxisomal morphology.…”

“…Next, the membrane of the elongated peroxisome forms constrictions by a not yet clearly defined mechanism [6]. Final fragmentation requires several fission proteins, including the tail-anchored (TA) proteins hFis1 (fission 1), Mff (mitochondrial fission factor) and the cytosolic Drp1/DLP1 (dynamin-related protein 1) [7][8][9][10][11][12]. These proteins are also essential fission factors at the mitochondrial outer membrane (MOM).…”

Dynamin-related Protein 1 (Drp1) Promotes Structural Intermediates of Membrane Division

“…Dynamin-related protein (Drp1), an 80-kDa mechanochemical GTPase of the dynamin superfamily, is required for both mitochondrial and peroxisomal fission in mammals (9,10). This protein shuttles between the cytosol and these organelles, where it is recruited to potential fission sites.…”

Interaction between peroxisomes and mitochondria in fatty acid metabolism

“…DRP1a and PEX11 proteins did not seem to interact directly but the isoform a of DRP1 and PEX11-beta are overexpressed during this process [28].…”