Research
Peroxisome Homeostasis In Yeast And Humans
We are interested in the problem of organelle homeostasis, using peroxisomes as the model organelle. Like all other subcellular organelles, peroxisomes and peroxisomal functions are indispensable for human survival. Our studies on peroxisome homeostasis examine how peroxisomes are assembled (biogenesis) and destroyed (turnover or pexophagy), as well as the coordination of these two processes within cells. We are also interested in the role of peroxisome biogenesis and turnover in disease states.

Peroxisome biogenesis: Work done in this and other labs has uncovered about 36 peroxins, encoded by PEX genes, involved in peroxisome biogenesis. Many proteins involved in this process are conserved in evolution from yeast to man, and inactivating mutations in at least half of these peroxins cause fatal human disorders (Zellweger syndrome, rhizomelic chondrodysplasia punctata and infantile Refsum disease). Work on peroxisome biogenesis is summarized in a review (Farré et al., EMBO Reports, 2018, PMID: 30530632).

Current work focuses on the trafficking of peroxisomal membrane proteins via the endoplasmic reticulum, their budding into pre-peroxisomal vesicles (ppV) and the proteins and mechanisms involved in this ppV budding.

Peroxisome degradation: Autophagy is a process in which cells eat themselves, especially under starvation conditions, and recycle cellular building blocks such as amino acids, lipids and sugars. Autophagy plays a key role in development, aging, neurodegeneration, cell death, cell survival, and innate immunity. While autophagy generally degrades cargoes non-selectively, it can also be adapted to degrade and recycle selective cargoes, including organelles and protein aggregates. Pexophagy is a turnover pathway in which redundant, damaged or unnecessary peroxisomes are selectively degraded by the autophagy machinery in response to specific environmental cues. Other selective autophagy pathways include mitophagy, ribophagy, ER-phagy, micronucleophagy and the Cvt pathway in yeasts. Progress in the field of selective autophagy may be found in a review (Farré et al., Nature Rev. Mol. Cell Biol., 2016, PMC5549613).