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Unexpected Link between Metal Ion Deficiency and Autophagy in Aspergillus fumigatus ^,

Department of Pathology & Laboratory Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0529,¹ Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461,² Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461,³ Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, New York 10461⁴

Received 25 June 2007/ Accepted 19 September 2007

Autophagy is the major cellular pathway for bulk degradation of cytosolic material and is required to maintain viability under starvation conditions. To determine the contribution of autophagy to starvation stress responses in the filamentous fungus Aspergillus fumigatus, we disrupted the A. fumigatus atg1 gene, encoding a serine/threonine kinase required for autophagy. The Afatg1 mutant showed abnormal conidiophore development and reduced conidiation, but the defect could be bypassed by increasing the nitrogen content of the medium. When transferred to starvation medium, wild-type hyphae were able to undergo a limited amount of growth, resulting in radial expansion of the colony. In contrast, the Afatg1 mutant was unable to grow under these conditions. However, supplementation of the medium with metal ions rescued the ability of the Afatg1 mutant to grow in the absence of a carbon or nitrogen source. Depleting the medium of cations by using EDTA was sufficient to induce autophagy in wild-type A. fumigatus, even in the presence of abundant carbon and nitrogen, and the Afatg1 mutant was severely growth impaired under these conditions. These findings establish a role for autophagy in the recycling of internal nitrogen sources to support conidiophore development and suggest that autophagy also contributes to the recycling of essential metal ions to sustain hyphal growth when exogenous nutrients are scarce.

Published ahead of print on 5 October 2007.

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