Alcohol dehydrogenase 1 acts as a scaffold protein in mitophagy essential for fungal pathogen adaptation to hypoxic niches within hosts.

Fungi have evolved diverse physiological adaptations to hypoxic environments. However, the mechanisms mediating such adaptations remain obscure for many filamentous pathogenic fungi. Here, we show that autophagy mediated mitophagy occurs in the insect pathogenic fungus Beauveria bassiana under hypoxic conditions induced by host cellular immune responses. Mitophagy was essential for fungal evasion from insect hemocyte encapsulation, allowing for fungal proliferation and colonization in the host hemocoel. Our data showed that B. bassiana autophagy-related protein 11 (Atg11) interacts with Atg8 as a scaffold mediating mitophagy. The mitochondrial protein Atg43 was demonstrated to act as a receptor for the selective mitophagy, directly interacting with Atg8 for the autophagosomal targeting. Alcohol dehydrogenase BbAdh1, as a novel scaffold protein, participates in mitophagy through interacting with Atg8 and Atg11 under hypoxic stress. BbAdh1 was critical for fungal intracellular redox homeostasis and energy metabolism under hypoxic conditions. These data provide a pathway for mitochondrial degradation via metabolism linked autophagosome- to-vacuole targeting during hypoxic stress. This mitophagy results in depletion of oxidative mitochondrial dependent functions as a cellular adaptation to the low oxygen levels.