Iron-depletion promotes mitophagy to maintain mitochondrial integrity in pathogenic yeast <i>Candida glabrata</i>

<p><i>Candida glabrata</i>, a haploid budding yeast, is the cause of severe systemic infections in immune-compromised hosts. The amount of free iron supplied to <i>C. glabrata</i> cells during systemic infections is severely limited by iron-chelating proteins such as transferrin. Thus, the iron-deficiency response in <i>C. glabrata</i> cells is thought to play important roles in their survival inside the host's body. In this study, we found that mitophagy was induced under iron-depleted conditions, and that the disruption of a gene homologous to <i>ATG32</i>, which is responsible for mitophagy in <i>Saccharomyces cerevisiae</i>, blocked mitophagy in <i>C. glabrata</i>. The mitophagic activity in <i>C. glabrata</i> cells was not detected on short-period exposure to nitrogen-starved conditions, which is a mitophagy-inducing condition used in <i>S. cerevisiae</i>. The mitophagy-deficient <i>atg32</i>Δ mutant of <i>C. glabrata</i> also exhibited decreased longevity under iron-deficient conditions. The mitochondrial membrane potential in <i>Cgatg32</i>Δ cells was significantly lower than that in wild-type cells under iron-depleted conditions. In a mouse model of disseminated infection, the <i>Cgatg32</i>Δ strain resulted in significantly decreased kidney and spleen fungal burdens compared with the wild-type strain. These results indicate that mitophagy in <i>C. glabrata</i> occurs in an iron-poor host tissue environment, and it may contribute to the longevity of cells, mitochondrial quality control, and pathogenesis.</p>