Parkin-independent mitophagy-FKBP8 takes the stage

Abstract

Although the Parkin/PINK1 pathway has received considerable attention in recent years as a key regulator of mitophagy in mammals, it is important to recognize that multiple mitophagy receptors like BNIP3, NIX, and FUNDC1 exist that can promote the selective clearance of mitochondria in the absence of Parkin. In this issue, Bhujabal et al expand the repertoire of Parkin-independent mitophagy receptors to include the anti-apoptotic protein, FKBP8. The authors demonstrate that FKBP8 interacts preferentially with LC3A via its LIR motif to destroy damaged mitochondria. During the process, FKBP8 escapes from the destruction presumably to prevent apoptosis during mitophagy [1].

Figure 1. FKBP8 recruits LC3A to mediate mitophagy

FKBP8 is normally localized to the outer membrane of the mitochondria. In response to mitochondrial depolarization, FKBP8 preferentially recruits the lipidated form of LC3A to initiate mitophagy. During the process, FKBP8 escapes to the endoplasmic reticulum to avoid being degraded, which is apparently important to prevent apoptosis from occurring during mitophagy.