Uth1p is involved in the autophagic degradation of mitochondria.
Ingrid Kissova (1), Maika Deffieu (2), Giséle Velours (2), Bénédicte Salin (2), Jacques Schaeffer (2), Stéphen Manon (2), Nadine Camougrand (2)
(1) Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-1, 84215 Bratislava, Slovak Republic; (2) UMR5095 CNRS/Université de Bordeaux 2, 33700 Bordeaux, France
The absence of the outer mitochondrial membrane protein Uth1p was found to induce resistance to rapamycin treatment and starvation, two conditions that induce the autophagic process. Biochemical studies showed the onset of a fully active autophagic activity both in wild-type and Δ uth1 strains. On the other hand, the disorganization of the mitochondrial network induced by rapamycin treatment or nitrogen starvation was followed in cells expressing mitochondria-targeted GFP; a rapid colocalization of GFP fluorescence with vacuole-selective fm4-64 labeling was observed in the wild-type but not in the Δ uth1 strain. Degradation of mitochondrial proteins, followed by Western blot analysis, did not occur in mutant strains carrying null mutations of the vacuolar protease Pep4p, the autophagy-specific protein Atg5p, and Uth1p. These data show that, although the autophagic machinery was fully functional in the absence of Uth1p, this protein is involved in the autophagic degradation of mitochondria. Furthemore, the addition of cAMP reverses the effect of Uth1p depletion causing once again the sensitivity to rapamycin and the degradation of mitochondria as was observed in the original wild-type. This work was supported by post-doctoral fellowship from the Fondation pour la Recherche Médicale (to I.K.).