53 Oral - Cell Biology I
Friday April 08, 9:45 AM - 10:00 AM

Authors:
Anastasia Minenkova ¹; Swathi Jeedigunta ¹; Jonathan Palozzi ¹; Yun Li ^1,2; Thomas Hurd ¹

Affiliations:
1) University of Toronto, Toronto, Ontario, Canada; 2) The Hospital for Sick Children, Toronto, Ontario, Canada

Keywords:
h. mitochondria; s. autophagy

Mitochondria are essential, intracellular energy-producing organelles that contain their own DNA (mtDNA). In metazoans, mtDNA is subject to high mutation rates, inherited uniparentally, and undergoes little recombination. This makes mtDNA prone to the accumulation of deleterious mutations, which can cause severe disease. To prevent deleterious mutations from being inherited, the female germline has evolved a conserved quality control mechanism, termed mtDNA selection. During this process, mitochondria with deleterious mutations are purged from the germline. The mechanism of mtDNA selection is poorly understood; however, we have recently identified that mitochondrial autophagy (mitophagy) is required for this process in Drosophila. We find that the outer mitochondrial membrane mitophagy receptor BNIP3 is required for both selection and mitophagy. BNIP3 mediates the incorporation of mitochondria into autophagosomes through the interaction with the core autophagy machinery component Atg8a through its LC3 interacting region (LIR). BNIP3 also plays a minor role in the de novo assembly of autophagosomes, which independent of its LIR. Together, our results suggest that BNIP3-mediated mitophagy represents a generalizable mechanism for selection against deleterious mtDNA mutations, which may enable the development of strategies for the treatment of mtDNA disorders.