Peroxisomal Biogenesis in Mammalian Cells The Historical Perspective for ER Participation

It became apparent in the 1970s that deficiencies in peroxisomal biogenesis were responsible for certain diseases, e.g. Zellweger syndrome, which is characterized by peroxisomal membrane ghosts in the human cells. These ghosts possessed membrane proteins, but were devoid of matrix proteins. Obviously, a direct relationship between a debilitating disease in humans and the biogenesis of a specific organelle (peroxisomes in this case) stimulated concerted research in this area. As a result, a model known as the ER vesicu-lation model emerged. It was characterized by the co-translational insertion of nascent proteins to the ER membrane and lumen followed by a pinching off of nascent peroxisomes. Electron microscopy studies that showed close associations of peroxisomes with profiles of rough ER in plant, animal, and yeast cells were often cited in support of this universal vesiculation model. However, plant biologists in particular, constantly pointed out that the peroxisome boundary membrane was not in direct continuity with ER membranes in a manner indicative of vesiculation from rough ER. Examples of such images are given in Trelease (2002, Fig. 1). Taken together, these contrary image interpretations and the lack of convincing evidence for co-translational import of proteins into peroxisomes, [discussed extensively at international meetings, see Kindl and Lazarow (1982), and in early reviews, see for example Trelease (1984)] led to this model falling out of favor in the early 1980s.

Lazarow and Fujiki published a most influential review in 1985. They effectively dismantled any remaining support for the ER vesiculation model, citing experimental evidence that peroxisomal proteins were synthesized on free ri-bosomes and inserted post-translationally into peroxisomes. They proposed a new model, referred to as the autonomous growth and division model, which excluded any participation of ER. This model is depicted using dashed lines in Fig. 1. For the next ten years or so, this model for peroxisome biogenesis became firmly entrenched in the literature encompassing all organisms, not just for mammals from whence the supporting data was derived. However, in 1996 Trelease (Muller and Trelease 1996) and Baker (1996) stated that growth and division was an oversimplification, i.e., that alternative scenarios such as division and growth, division without growth, and growth without division were known. Unfortunately, these two papers had little impact at the time.

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