Mitochondrial peroxiredoxin functions as crucial chaperone reservoir inLeishmania infantum

• DOI: 10.1073/pnas.1419682112
• Publication Date: 2015-02-03T04:18:45Z
• Authors: Filipa Teixeira; Helena Castro; Tânia Cruz; Eric Tse; Philipp Koldewey; Daniel R. Southworth; Ana M. Tomás; Ursula Jakob
• Keywords: Leishmania; Leishmania infantum/pathogenicity; Protein Folding; 0303 health sciences; Molecular Chaperones/metabolism; Virulence; peroxiredoxin; Peroxiredoxins; Biological Sciences; Luciferases/metabolism; Vector-Borne Diseases; 03 medical and health sciences; Emerging Infectious Diseases; Infectious Diseases; Good Health and Well Being; chaperone; Animals; Peroxiredoxins/metabolism; Biochemistry and Cell Biology; Leishmania infantum/enzymology; Leishmania infantum; Infection; Luciferases; Molecular Chaperones

SignificancePeroxiredoxins (Prxs) are highly abundant proteins, which serve two seemingly mutually exclusive roles as peroxidases and molecular chaperones. Little is known about the precise mechanism of Prxs’ activation as chaperone and the physiological significance of this second function. Here we demonstrate that inLeishmania infantum, reduced Prx provides a crucial, stress-specific chaperone reservoir, which is activated rapidly upon exposure to unfolding stress conditions. Once activated, Prx protects a wide range of different clients against protein unfolding. Clients are bound in the center of the decameric ring, providing experimental evidence for previous claims that Prxs serve as likely ancestors of chaperonins. Interference with client binding impairsLeishmaniainfectivity, providing compelling evidence for the in vivo importance of Prx’s chaperone function.