Neuronal induction of BNIP3-mediated mitophagy slows systemic aging in Drosophila

Abstract

The effects of aging on the brain are widespread and can have dramatic implications on the overall health of an organism. Mitochondrial dysfunction is a hallmark of brain aging, but the interplay among mitochondrial quality control, neuronal aging and organismal health is not well understood. Here, we show that aging leads to a decline in mitochondrial autophagy (mitophagy) in the Drosophila brain with a concomitant increase in mitochondrial content. We find that induction of BCL2-interacting protein 3 (BNIP3), a mitochondrial outer membrane protein, in the adult nervous system induces mitophagy and prevents the accumulation of dysfunctional mitochondria in the aged brain. Importantly, neuronal induction of BNIP3-mediated mitophagy increases organismal longevity and healthspan. Furthermore, BNIP3-mediated mitophagy in the nervous system improves muscle and intestinal homeostasis in aged flies, indicating cell nonautonomous effects. Our findings identify BNIP3 as a therapeutic target to counteract brain aging and prolong overall organismal health with age.