Iron-depletion promotes mitophagy to maintain mitochondrial integrity in pathogenic yeast Candida glabrata. Issue 8 (2nd August 2016)

• Record Type: Journal Article
• Authors: Nagi, Minoru; Tanabe, Koichi; Nakayama, Hironobu; Ueno, Keigo; Yamagoe, Satoshi; Umeyama, Takashi; Ohno, Hideaki; Miyazaki, Yoshitsugu
• Is Part Of: Autophagy. Volume 12:Issue 8(2016)
• Page Start: 1259
• Page End: 1271
• Publication Date: 2016-08-02
• Subjects: Atg32 -- autophagy -- Candida -- iron -- mitochondria -- mitophagy -- pathogenicity -- yeast; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2016.1183080
• Languages: English
• ISSNs: 1554-8627

Abstract

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