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. Author manuscript; available in PMC: 2021 Jan 23.
Published in final edited form as: Cell. 2020 Jan 23;180(2):296–310.e18. doi: 10.1016/j.cell.2019.12.035

Figure 7. Amino Acid Driven Iron Limitation Links Vacuoles and Mitochondria in Aging.

Figure 7.

(A) Flow cytometry analysis of FIT2pr-GFP expression in young (Y) and old (O) cells grown +/− Fe. Bars = mean ± SD, n=3. Mean ages (divisions): Y = 1, O = 13. See Star Methods for age determination.

(B) Flow cytometry analysis of FIT2pr-GFP expression in young and old cells containing either empty vector or overexpressing AVT1. Bars = mean ± SD, n=3. Mean ages: Y = 1, O = 12.

(C) Flow cytometry analysis of FIT2pr-driven GFP expression in young and old cells cultured in the indicated medium. Bars = mean ± SD, n=3. Mean ages: Y = 1, O = 13.

(D) Flow cytometry analysis of FIT2 promoter-driven GFP expression in young and old cells cultured in low amino acid medium +/− excess cysteine or threonine. Bars = mean ± SD, n=3. Mean ages: Y = 1, O = 13.

(E) Maximum-intensity projection images showing yeast mitochondrial structure (Tom70-GFP) in young and old cells grown +/− Fe. For (E–G): scale bar = 5 μm, percentage of cells with fragmented or aggregated mitochondria is indicated (n=100 cells), and mean age (determined by bud scar counting) is indicated in bottom panels showing calcofluor-stained bud scars.

(F) Maximum-intensity projection images showing yeast mitochondrial structure in young and old cells cultured in the indicated medium.

(G) Maximum-intensity projection images showing yeast mitochondrial structure in young and old cells cultured in low amino acid medium +/− excess cysteine.

(H) (Top) In young cells, the V-ATPase-dependent proton gradient is harnessed by amino acid/proton antiporters to compartmentalize cysteine within vacuoles. Cysteine compartmentation ensures iron availability for ISC (Fe-S) dependent mitochondrial respiration. (Bottom) In aged yeast, the pH of the vacuole increases, blocking cysteine storage. Elevated non-vacuolar cysteine promotes ROS, which disrupts iron homeostasis and mitochondrial respiration.