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Recycling of iron via autophagy is critical for the transition from glycolytic to
respiratory growth
#MMPMID28320861
Horie T
; Kawamata T
; Matsunami M
; Ohsumi Y
J Biol Chem
2017[May]; 292
(20
): 8533-8543
PMID28320861
show ga
Autophagy is a bulk degradation process conserved from yeast to mammals. To
examine the roles of autophagy in cellular metabolism, we generated
autophagy-defective (atg) mutants in the X2180-1B strain background. We compared
the growth of wild-type (WT) and atg cells in minimal (synthetic dextrose, SD)
and rich (yeast extract/peptone/dextrose, YEPD) medium, and we found that
mutations in the core autophagy machinery result in defects in the diauxic shift,
the transition from fermentation to respiratory growth upon glucose depletion,
specifically in SD. Furthermore, we confirmed that autophagy was induced prior to
the diauxic shift, implying that it plays a role in this process. In YEPD, atg
mutants grew normally, so we assumed that the insufficiency of certain nutrients
in SD was responsible for the defects. We ultimately identified iron, which is a
necessary cofactor for respiratory activity, as the nutrient required for the
diauxic shift in atg mutants. Indeed, atg mutants exhibited defects in
respiration, which was rescued by supplementation with iron. Based on these data,
we hypothesized that autophagy is involved in iron recycling during the diauxic
shift. smf3?fet5? or smf3?ftr1? cells, which are unable to export iron from the
vacuole, also exhibit defects in the diauxic shift, so iron released from the
vacuole is important for the shift in SD medium. Finally, we observed that
smf3?fet5? cells accumulated nearly twice as much vacuolar iron as
smf3?fet5?atg2? cells, suggesting that autophagy is involved in iron recycling by
the vacuolar transport and degradation of iron-containing cargos.