REDOX-SENSITIVE HOMODIMERIZATION OF PEX11P - A PROPOSED MECHANISM TO REGULATE PEROXISOMAL DIVISION

Pex11p (formerly Pmp27) has been implicated in peroxisomal proliferati on (Erdmann, R., and G. Blobel. 1995. J. Cell Biol. 128: 509-523; Mars hall, P.A., Y.I. Krimkevich, R.H. Lark, J.M. Dyer, M. Veenhuis, and J. M. Goodman. 1995. J. Cell Biol. 129:345-355). In its absence, peroxiso mes in Saccharomyces cerevisiae fail to proliferate in response to ole ic acid; instead, one or two large peroxisomes are formed. Conversely, overproduction of Pex11p causes an increase in peroxisomal number. In this report, we confirm the function of Pex11p in organelle prolifera tion by demonstrating that this protein can cause fragmentation in viv o of large peroxisomes into smaller organelles. Pex11p is on the inner surface of the peroxisomal membrane. It can form homodimers, and this species is more abundant in mature peroxisomes than in proliferating organelles. Removing one of the three cysteines in the protein inhibit s homodimerization. This cysteine 3 --> alanine mutation leads to an i ncrease in number and a decrease in peroxisomal density, compared with the wild-type protein, in response to oleic acid. We propose that the active species is the ''monomeric'' form, and that the increasing oxi dative metabolism within maturing peroxisomes causes dimer formation a nd inhibition of further organelle division.