Quality control of ABCD3 by the VCP-FAF2 complex suppresses excessive pexophagy.

Abstract

Peroxisomes play many crucial roles in cells such as the oxidation of very long-chain fatty acids and the detoxification of hydrogen peroxide. Given that peroxisomes are constantly exposed to various stresses, it is reasonable to assume that peroxisomes undergo robust quality- and quantity-control. Although the molecular mechanisms of this control remain to be fully elucidated, we recently demonstrated that the VCP-FAF2 complex plays a pivotal role in peroxisomal maintenance. More specifically, we found that the complex prevents excessive selective autophagic peroxisomal degradation (pexophagy) by regulating the accumulation of the ubiquitinated form of peroxisomal membrane protein ABCD3.Abbreviation: ABCD3: ATP binding cassette subfamily D member 3, CALCOCO2: calcium binding and coiled-coil domain 2, FAF2: Fas associated factor family member 2, OPTN: optineurin, RB1CC1: RB1 inducible coiled-coil 1, SQSTM1: sequestosome 1, TAX1BP1: Tax1 binding protein 1, UBA domain: ubiquitin-associated domain, VCP: valosin containing protein.