The GSNOR1-VDAC3 complex acts as a cargo co-receptor for mitophagy in response to mitochondrial stress in plants

Abstract

Mitochondria are central for cellular energy metabolism, and their quality is warranted by multiple mechanisms, including mitophagy, a process of selectively removing damaged, aged, or excess mitochondria. However, the regulatory mechanism of mitophagy remains elusive in plants. Here, we report that Arabidopsis S-nitrosoglutathione reductase 1 (GSNOR1), an enzyme that has long been known to degrade S-nitrosoglutathione, interacts with the outer mitochondrial membrane protein Voltage-Dependent Anion Channel 3 (VDAC3) to mediate mitophagy. GSNOR1 translocates to depolarized mitochondria, binds to VDAC3, and interacts with Autophagy-related 8 (ATG8) via its ATG8-interacting motifs, thereby engulfing damaged mitochondria in autophagosomes for mitophagic degradation. Mutations in GSNOR1 or VDAC3 cause the accumulation of misshapen mitochondria and hypersensitivity to mitochondrial stress. We propose that GSNOR1 acts as a cargo receptor interacting with VDAC3 and ATG8 to target depolarized mitochondria to mitophagy, thereby regulating cellular homeostasis.