Import Oligomers Induce Positive Feedback to Promote Peroxisome Differentiation and Control Organelle Abundance

A fundamental question in cell biology is how cells control organelle composition and abundance. Woronin bodies are fungal peroxisomes centered on a crystalline core of the self-assembled HEX protein. Despite using the canonical peroxisome import machinery for biogenesis, Woronin bodies are scarce compared to the overall peroxisome population. Here, we show that HEX oligomers promote the differentiation of a subpopulation of peroxisomes, which become enlarged and highly active in matrix protein import. HEX physically associates with the essential matrix import peroxin, PEX26, and promotes its enrichment in the membrane of differentiated peroxisomes. In addition, a PEX26 mutant that disrupts differentiation produces increased numbers of aberrantly small Woronin bodies. Our data suggest a mechanism where HEX oligomers recruit a key component of the import machinery, which promotes the import of additional HEX. This type of positive feedback provides a basic mechanism for the production of an organelle subpopulation of distinct composition and abundance. [Display omitted] ► Differentiated peroxisomes receive the majority of nascent matrix protein import ► The Woronin body scaffold HEX recruits the matrix import peroxin, PEX26 ► This interaction enables a feedback loop that drives Woronin body differentiation ► Thus, peroxisome differentiation is coupled to subcompartment size and abundance