Abstract
The maintenance of healthy mitochondria is essential to neuronal homeostasis. Mitophagy is a critical mechanism that degrades damaged mitochondria, and disruption of this process is associated with neurodegenerative disease. Previous work has shown that mammalian optineurin (OPTN), a gene mutated in familial forms of amyotrophic lateral sclerosis (ALS) and glaucoma, is an adaptor to recruit autophagy machinery to mitochondria for ubiquitin-dependent mitophagy in cultured cells. However, OPTN's role in neuronal mitophagy in vivo remains largely unknown. Here, we demonstrate that the Drosophila autophagy adaptor gene Kenny, a homologue of OPTN, mediates the recruitment of the phagophore to mitochondria undergoing ubiquitin-dependent mitophagy. We find that Kenny colocalizes with ubiquitinated mitochondria targeted for autophagic degradation in larval motoneurons, and is concentrated on the mitochondrial surface in areas opposed to the phagophore. Removal of Kenny in conditions of induced mitophagy eliminates the recruitment of the phagophore to ubiquitinated mitochondria and decreases mitophagic flux. In basal conditions, loss of Kenny causes accumulation of ubiquitinated mitochondria in neurons, indicative of stalled mitophagy. These phenotypes were reproduced in Kenny mutants, ablating the LC3-interacting region domain. Overall, this work establishes Kenny as a functional homologue of OPTN in flies and a mediator of neuronal mitophagy in vivo.
