Voltage-dependent anion channels are mitophagy receptors mediating the recycling of depolarized mitochondria in Arabidopsis

Abstract

The mitochondrion is an essential organelle in eukaryotic cells, playing crucial roles in cellular respiration and intracellular signaling pathways. To maintain a healthy population of mitochondria, dysfunctional and excess mitochondria are selectively removed through an autophagic process known as mitophagy. Over the past few decades, various autophagy-related (ATG) proteins involved in mitophagy have been well characterized in yeast and mammalian cells since it has significance to the survival of eukaryotes. While the core autophagy machinery responsible for autophagosome formation is conserved among eukaryotes, the homologs of key regulators of mammalian system is absent in plant. In this study, we identified a unique mitophagy mechanism in plant, that three voltage-dependent anion channel (VDAC) family proteins in the mitochondria outer membrane -- specifically VDAC1, VDAC2, and VDAC3 -- as mitophagy receptors in Arabidopsis. These proteins were required for translocation of ATG8 from the cytosol to the mitochondria surface, when Arabidopsis cells were treated with an uncoupler, 2,4-dinitrophenol (DNP). The VDACs interacted directly with ATG8 through an ATG8-interacting motif (AIM) located in their amino (N) termini. Furthermore, vdac mutants exhibited impaired uncoupler-induced mitophagy and accumulated damaged mitochondria. These mitophagy-related phenotypes were more pronounced in vdac double and triple mutant lines. Altogether, our results indicated that VDAC1, 2, and 3 recruit ATG8 to depolarized mitochondria, facilitating the formation of mitophagosomes, presenting a distinguishing mitophagy pathway with mammalian system.