Incredibly close-A newly identified peroxisome-ER contact site in humans

Abstract

Peroxisomes are tiny organelles that control important and diverse metabolic processes via their interplay with other organelles, including the endoplasmic reticulum (ER). In this issue, Costello et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607055) and Hua et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608128) identify a peroxisome-ER contact site in human cells held together by a tethering complex of VAPA/B (vesicle-associated membrane protein-associated proteins A/B) and ACBD5 (acyl Co-A binding protein 5).

Figure 1.

The peroxisomal ACBD5 protein and the VAPA/B ER proteins mediate a physical peroxisome–ER contact in humans. ACBD5 and the VAPA and VAPB proteins are anchored to the peroxisome or to the ER membrane, respectively, through a transmembrane domain localized at their C’ termini, whereas their N’ termini face the cytosol. The VAP–ACBD5 interaction is mediated through the FFAT motif of ACBD5 and the MSP domain of the VAP proteins. Together the proteins form a tether complex that holds the peroxisome and ER membranes in close proximity. The physical contact is suggested to enable ER-to-peroxisome transport of lipids, required for elongation and growth of the peroxisome membrane, as well as peroxisome-to-ER transport of plasmalogen and cholesterol precursors. Because other cellular contacts are held by more than a single tether, additional tethering complexes (proteins marked in gray) might be discovered in the future.