A novel regulator of selective autophagy: TNIP1/ABIN-1 modulates mitophagy.

Abstract

TNIP1/ABIN-1 is a novel inhibitor of inflammation and cell death. In our study, we elucidated the MAP1LC3/LC3 (microtubule associated protein 1 light chain 3)-interacting region (LIR) 1 and 2 motifs of TNIP1-dependent direct binding to LC3B-II and subsequent colocalization on phagophores. In addition, TNIP1 colocalizes with LAMP1 (lysosomal associated membrane protein 1) on autolysosomes. Autophagic stimuli induce the translocation of TNIP1 to damaged mitochondria promoting the degradation of the mitochondrial outer membrane proteins VDAC1 (voltage dependent anion channel 1), MFN2 (mitofusin 2), and TOMM20 (translocase of outer mitochondrial membrane 20), together with its own degradation, possibly via the autophagic pathway. Knockdown of TNIP1 partially but significantly inhibits mitophagy. Thus, identification of TNIP1 as a novel selective mitophagy regulator promoting mitophagy would play a decisive role in understanding the pathophysiological outcome associated with diverse types of mitochondria-associated cellular stress.