Pichia pastoris Rppa09976 is a peroxisomal membrane- associated ACBP domain-containing protein, delivered to peroxisomes from the ER, and is required for their selective degradation
- Author(s): Ozeki, Katharine
- et al.
It is imperative for organisms to find a way to recycle and degrade cytoplasmic constituents and eliminate unnecessary organelles. Autophagy is a tightly-regulated, non-selective degradation process that plays an integral role in cellular homeostasis by sequestering ubiquitous proteins or organelles, and delivers such cargo to the vacuole so that they may be degraded and their constituents recycled. For instance, peroxisomes are single membrane-bound organelles required for certain metabolic pathways including both alpha- and beta- oxidation of fatty acids, decomposition of harmful hydrogen peroxide molecules, the production of penicillin in certain fungi and photorespiration in plants. When peroxisomes become redundant, they are selectively delivered to the vacuole in an autophagy-related pathway, termed pexophagy. While most proteins required for autophagy are also required for pexophagy, only two proteins, Atg26 and Atg30, are known to be solely required for pexophagy, but not autophagy-related pathways. Here, we identified a novel peroxisomal membrane-associated acyl -CoA binding protein (ACBP) domain-containing protein, Rppa09976, also required for the selective degradation of peroxisomes, but dispensable for other autophagy-related pathways. Unlike most peroxisomal membrane proteins, Rppa09976 is a type II PMP, trafficking from the ER to peroxisomes, and degrades independent of pexophagy, autophagy and vacuolar proteolysis. Furthermore, we have identified a putative mammalian homolog, the murine peroxisomal MmAcbd5 protein, which, like Rppa09976, contains an N-terminal acyl-CoA binding protein (ACBP) domain. This discovery has led to a deeper understanding of the mechanism underlying the selective sequestration and degradation of peroxisomes, a process that may apply to higher organisms.